Revisiting Epigenetics Fundamentals and Its Biomedical Implications

May combine two claims.

In mammalian somatic cells, DNA methylation occurs predominantly in 98% of 5'CpG3' dinucleotides; in embryonic stem cells, only 75% of CpG dinucleotides are methylated.

“In mammalian somatic cells, this modification occurs predominantly in 98% of 5’CpG3’ dinucleotides; on the other hand, in embryonic stem cells, only 75% of CpG dinucleotides are methylated.”

• cites [53] Kim, 2021, Multi-omics integration Strategies for animal Epigenetic studies, Anim. Biosci. sourceDisputed

  The DNA methylation section gives the percentages as the share of DNA methylation that occurs at CpG sites: 98% in mammalian somatic cells and 75% in embryonic stem cells. The claim instead presents them as the share of CpG dinucleotides that are methylated. The same section says 60%–80% of CpGs in the human genome are methylated. (LLM, conf=0.90)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

In mammals, DNMT1 has been identified as de novo methyltransferase, whereas DNMT3A and DNMT3B are maintenance methyltransferases.

“In mammals, DNMT1 has been identified as de novo methyltransferase, whereas DNMT3A and DNMT3B are maintenance methyltransferases.”

• cites [55] Melamed, P., Yosefzon, Y., David, C., Tsukerman, A., and Pnueli, L. (2018). TET Enzymes, variants, and differential effects on function. Front. Cell Dev. Biol., 6. sourceDisputed

  In “The TET enzymes, DNA hydroxymethylation, and demethylation” (page unavailable), the paper says DNMT1 is recruited to hemimethylated CpG during DNA replication, contrary to the claim’s assignment of DNMT1 to de novo methylation. Its References section (page unavailable) also identifies DNMT1 as a maintenance methyltransferase. The retrieved passages do not address the claimed roles of DNMT3A and DNMT3B. (LLM, conf=0.86)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The first level of chromatin organization is the nucleosome, composed of two copies of histones, which are the core protein components of the chromatin complex.

“The first level of chromatin organization is known as the nucleosome, and it is composed of two copies of histones, which are the core protein components of the chromatin complex.”

• cites [53] Kim, 2021, Multi-omics integration Strategies for animal Epigenetic studies, Anim. Biosci. sourcePartly supported

  The Histone modification section identifies the nucleosome as the first level of chromatin organization and histones as core proteins of chromatin. But it specifies two copies *each* of H2A, H2B, H3, and H4—eight histone proteins in the core—not simply two copies of histones. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

Nucleosomes are unstable, and their structure changes rapidly in response to external stimuli, leading to permanent changes in chromosome organization, exhibiting heterochromatin and euchromatin domains.

“Nucleosomes are unstable, and their structure changes rapidly in response to external stimuli, leading to permanent changes in the organization of chromosomes, thus exhibiting different domains, such as heterochromatin and euchromatin, that are defined by their degree of compaction and are associated with gene functionality [57].”

• cites [57] McGinty, 2014, Nucleosome structure and function, Chem. Rev. sourcePartly supported

  The Introduction describes nucleosomes as units of chromatin compaction and says histone modifications can tune nucleosome stability and higher-order compaction. It also links coordinated accessibility to transcriptional activity and repression. It does not say nucleosomes are generally unstable or that external stimuli rapidly change their structure and cause permanent chromosome reorganization; the cited passages do not define heterochromatin and euchromatin domains. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

The epigenetic landscape is a platform for interaction of a variety of environmental factors with a complex genetic environment to change gene expression.

“the term epigenetic landscape is defined as a platform for the interaction of a variety of environmental factors with a complex genetic environment to change the expression of genes [29,30,31].”

• cites [29] Goldberg, 2007, Epigenetics: A landscape takes shape, Cell sourcePartly supported

  The paper’s Abstract links changes in the “epigenetic landscape” to distinct, stable patterns of gene expression. It does not define that landscape as a platform where environmental factors interact with a complex genetic environment, so that part of the attributed definition is unsupported. (LLM, conf=0.85)

  Experimental — accuracy not yet measured
• cites [30] Waddington, C.H. (1939). An Introduction to Modern Genetics, The Macmillan Company. sourceNot checked — no full text of the source
• cites [31] Waddington, 1942, The epigenotype, Int. J. Epidemiol. sourceNot checked — no full text of the source

May combine two claims.

Histone methylation occurs in lysine and arginine residues in histone tails, where histone methyltransferases transfer a methyl group from SAM; demethylation is orchestrated by histone demethylases.

“Histone methylation occurs in lysine and arginine residues in histone tails, where histone methyltransferases transfer to a methyl group from a donor, SAM; demethylation is orchestrated by histone demethylases.”

• cites [55] Melamed, P., Yosefzon, Y., David, C., Tsukerman, A., and Pnueli, L. (2018). TET Enzymes, variants, and differential effects on function. Front. Cell Dev. Biol., 6. sourcePartly supported

  In “Different effects of different isoforms?” (page unavailable), the paper mentions H3K36 methyltransferases and their enzymatic activity, providing limited support for histone methylation by methyltransferases. It does not describe arginine methylation, SAM as the methyl donor, or histone demethylases; its demethylation discussion concerns DNA cytosine instead. (LLM, conf=0.78)

  Experimental — accuracy not yet measured

May combine two claims.

TET enzymes (10-11 translocases), which are monooxygenases, mediate sequential oxidation of 5mC, and together with single-base excision, DNA repair machinery, and thymine DNA glycosylase (TDG) demethylases DNA.

“On the other hand, a group of enzymes called TET (10–11 translocases), which are monooxygenases, mediate the sequential oxidation of 5mC, and together with single-base excision, DNA repair machinery, and thymine DNA, glycosylase (TDG) demethylases DNA [55].”

• cites [55] Melamed, P., Yosefzon, Y., David, C., Tsukerman, A., and Pnueli, L. (2018). TET Enzymes, variants, and differential effects on function. Front. Cell Dev. Biol., 6. sourcePartly supported

  The section “The TET enzymes, DNA hydroxymethylation, and demethylation” describes sequential oxidation of 5mC, followed by TDG excision and base excision repair to complete active demethylation. However, it calls TET enzymes ten-eleven translocation methylcytosine dioxygenases, not “translocases” or monooxygenases. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

DNA methylation consists of the covalent addition of a methyl group (-CH3) to carbon five of the pyrimidine ring of cytosine, resulting in 5-methylcytosine (5 mC).

“This mechanism consists of the covalent addition of a methyl group (-CH3) to carbon five of the pyrimidine ring of cytosine, resulting in 5-methylcytosine (5 mC) [53].”

• cites [53] Kim, 2021, Multi-omics integration Strategies for animal Epigenetic studies, Anim. Biosci. sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

DNA methylation can occur in non-CpG dinucleotides, such as CpA, CpT, or CpC.

“However, there is evidence that the methylation of DNA can occur in non-CpG dinucleotides, such as CpA, CpT, or CpC [53].”

• cites [53] Kim, 2021, Multi-omics integration Strategies for animal Epigenetic studies, Anim. Biosci. sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

Even in prokaryotes, there is evidence of histones H2A and H4 being responsible for the early emergence of a broad occurring structure in eukaryotes.

“For the case of histone modifications, even in prokaryotes, there is evidence of histones H2A and H4 being responsible for the early emergence of a broad occurring structure in eukaryotes [56].”

• cites [56] Slesarev, 1998, Evidence for an early prokaryotic origin of histones H2A and H4 prior to the emergence of eukaryotes, Nucleic Acids Res. sourcePartly supported

  The Introduction reports that a prokaryotic histone in Methanopyrus kandleri has a domain closely related to eukaryotic H2A and H4 and may represent an evolutionary step toward eukaryotic histones. The Results and Discussion also suggest that elements of eukaryotic DNA packaging predated eukaryotes. The paper does not establish that H2A and H4 were responsible for the emergence of a widespread eukaryotic structure; its evolutionary conclusion is more cautious. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Histones H2A, H2B, H3, and H4 are assembled in the nucleus as an octamer core surrounded by DNA.

“Histones H2A, H2B, H3, and H4 are assembled in the nucleus, as an octamer core surrounded by DNA.”

• cites [53] Kim, 2021, Multi-omics integration Strategies for animal Epigenetic studies, Anim. Biosci. sourceSupported

May combine two claims.

Acetylation occurs in N-terminal lysine residues of histones and is mediated by acetyltransferases (HATs) that add acetyl groups to histone tails.

“Acetylation occurs in the N-terminal lysine residues of histones, and this mechanism is mediated by acetyltransferases (HATs) that are responsible for adding acetyl groups to the tails of histones.”

• cites [55] Melamed, P., Yosefzon, Y., David, C., Tsukerman, A., and Pnueli, L. (2018). TET Enzymes, variants, and differential effects on function. Front. Cell Dev. Biol., 6. sourceCould not verify

  The section “The TET enzymes, DNA hydroxymethylation, and demethylation” describes TET-mediated DNA modification, not histone acetylation (page unavailable). Searches for HATs, N-terminal histone lysines, and acetylation of histone tails found no passage in our copy addressing the claim. (LLM, conf=0.76)

  Experimental — accuracy not yet measured
• cites [58] Chen, 2017, Epigenetic regulation: A new frontier for biomedical engineers, Annu. Rev. Biomed. Eng. sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

There is an external histone to the octamer known as the linker histone or H1 that participates in compaction of nucleosomes.

“There is an external histone to the octamer known as the linker histone or H1 that participates in the compaction of the nucleosomes [53].”

• cites [53] Kim, 2021, Multi-omics integration Strategies for animal Epigenetic studies, Anim. Biosci. sourcePartly supported

  The Histone modification section identifies the nucleosome’s octameric core as containing H2A, H2B, H3, and H4, which supports the claim that H1 is not part of the octamer. It does not identify H1 as a linker histone or say that H1 participates in nucleosome compaction (page unavailable). (LLM, conf=0.82)

  Experimental — accuracy not yet measured

May combine two claims.

DNA methylation can remodel chromatin structure and inhibit transcription and subsequent gene expression.

“Also, it can remodel the chromatin structure and inhibit transcription and subsequent gene expression [53].”

• cites [53] Kim, 2021, Multi-omics integration Strategies for animal Epigenetic studies, Anim. Biosci. sourceSupported

May combine two claims.

Acetylation neutralizes the positive charge of lysine by adding the acetyl group to histones, forming an affinity between DNA and histones less tightly arranged, and consequently greater accessibility of DNA to transcription factors.

“Firstly, it refers to the ability to neutralize the positive charge of the lysine by adding the acetyl group to histones, thus forming an affinity between DNA (negatively charged) and histones less tightly arranged, and consequently, greater accessibility of DNA to transcription factors is observed, for example.”

• cites [55] Melamed, P., Yosefzon, Y., David, C., Tsukerman, A., and Pnueli, L. (2018). TET Enzymes, variants, and differential effects on function. Front. Cell Dev. Biol., 6. sourceCould not verify

  The section ‘The TET enzymes, DNA hydroxymethylation, and demethylation’ discusses DNA hydroxymethylation and its association with transcription, not histone acetylation. Searches for lysine charge neutralization, weakened DNA–histone binding, and transcription-factor accessibility found no passage addressing the claimed mechanism; page numbers were unavailable in our copy. (LLM, conf=0.76)

  Experimental — accuracy not yet measured
• cites [58] Chen, 2017, Epigenetic regulation: A new frontier for biomedical engineers, Annu. Rev. Biomed. Eng. sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

70% of the promoters of total protein-coding genes are associated with CpG islands, and most of these sequences are demethylated.

“On the other hand, 70% of the promoters of the total protein-coding genes are associated with CpG islands, and most of these sequences are demethylated [54].”

• cites [54] Kim, 2017, DNA methylation: An epigenetic mark of cellular memory, Exp. Mol. Med. sourcePartly supported

  The DNA methylation section says approximately 70% of annotated gene promoters are associated with CpG islands and that these islands are largely resistant to DNA methylation. It does not specify protein-coding genes as the denominator for the 70% figure. (LLM, conf=0.83)

  Experimental — accuracy not yet measured

May combine two claims.

DNA methylation is highly relevant during X chromosome inactivation, genomic imprinting, chromosome stability maintenance, and suppression of repetitive elements in the genome.

“In addition, DNA methylation is highly relevant during X chromosome inactivation, genomic imprinting, chromosome stability maintenance, and the suppression of repetitive elements in the genome [53].”

• cites [53] Kim, 2021, Multi-omics integration Strategies for animal Epigenetic studies, Anim. Biosci. sourceSupported

May combine two claims.

DNA methylation plays an important role in regulation of gene expression, where methylation of CpG islands and promoters is a recognition platform for transcription factors or proteins that recruit factors.

“DNA methylation plays an important role in different molecular mechanisms, such as the regulation of gene expression, where the methylation of CpG islands and promoters is a recognition platform for different transcription factors or proteins that recruit different factors.”

• cites [53] Kim, 2021, Multi-omics integration Strategies for animal Epigenetic studies, Anim. Biosci. sourcePartly supported

  The DNA methylation section (page not provided) says methylated CpG islands can inhibit transcription and that DNA methylation has a functional role in transcriptional regulation. The DNA methylation profiling section also describes a protein that binds methylated CpG. Neither passage establishes the more specific claim that methylated CpG islands and promoters serve as a recognition platform for transcription factors or proteins that recruit other factors. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

In the human genome, between 60% and 80% of the total CpG dinucleotide content (29 million sites) is methylated.

“Interestingly, in the human genome, between 60% and 80% of the total CpG dinucleotide content (29 million sites) is methylated, and these sites are associated with repetitive sequences, transposable elements, and tissue-specific gene promoters.”

• cites [54] Kim, 2017, DNA methylation: An epigenetic mark of cellular memory, Exp. Mol. Med. sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

Transgenerational epigenetic stability has been defined differently, from intergenerational epigenetic inheritance (direct heritage from parents to children) to transgenerational inheritance (descending from F0 to F2, grandparents to grandchildren).

“Additionally, transgenerational epigenetic stability [44,49,50] has been defined differently, from intergenerational epigenetic inheritance, which represents the direct heritage of epigenetic marks from one generation to the next, which means directly from parents to children, to transgenerational inheritance, which has been defined as descending from F0 to F2, in other words, from grandparents to”

• cites [43] Michels, 2016, Transgenerational epigenetic inheritance in mammals: How good is the evidence?, FASEB J. sourceNot checked — no full text of the source
• cites [44] Pang, 2017, Transgenerational paternal transmission of acquired traits: Stress-induced modification of the sperm regulatory transcriptome and offspring phenotypes, Curr. Opin. Behav. Sci. sourcePartly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured
• cites [50] Skinner, 2008, What is an epigenetic transgenerational phenotype?, Reprod. Toxicol. sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

lncRNAs are molecules of 200 or more nucleotides in length and can originate from a sense or antisense form depending on their proximity to protein-coding genes.

“lncRNAs are a different type of molecule of 200 or more nucleotides in length, and can originate from a sense or antisense form, depending on their proximity to the genes that encode proteins.”

• cites [53] Kim, 2021, Multi-omics integration Strategies for animal Epigenetic studies, Anim. Biosci. sourceSupported
• cites [61] Winkle, 2021, Noncoding RNA therapeutics—Challenges and potential solutions, Nat. Rev. Drug Discov. sourcePartly supported

  The Introduction describes lncRNAs as transcripts longer than 200 nucleotides and identifies natural antisense transcripts as lncRNAs transcribed opposite coding genes. It does not describe a corresponding sense form or classify lncRNAs by their proximity to protein-coding genes. It also specifies >200 nucleotides, rather than 200 or more. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

May combine two claims.

piRNAs lead PIWI proteins to degrade specific targets recognized by complementary RNA sequence, or to methylate DNA, modify histones, or contribute to chromatin opening.

“piRNAs lead PIWI proteins to degrade any specific target, recognized by the complementary RNA sequence, or even to methylate DNA, histone modification, or contribute to chromatin opening.”

• cites [70] Zhang, 2011, A k-mer scheme to predict piRNAs and characterize locust piRNAs, Bioinformatics sourcePartly supported

  The Introduction (page unavailable) says piRNAs form complexes with PIWI proteins, supporting their association. It does not say that piRNAs guide PIWI proteins to complementary targets for degradation, or that they cause DNA methylation, histone modification, or chromatin opening; searches for those mechanisms found no supporting passage. (LLM, conf=0.83)

  Experimental — accuracy not yet measured

May combine two claims.

eRNAs are medium in length (<2 kb), related to transcriptional regulation, and their central role is in promoter modulation, mediating the link between the enhancer and the promoter.

“eRNAs are medium in length (<2 kb) and are related to transcriptional regulation, and their central role is in promoter modulation, mediating the link between the enhancer and the promoter [75].”

• cites [75] Rahnamoun, 2019, The role of enhancer RNAs in epigenetic regulation of gene expression, Transcription sourcePartly supported

  The passage labeled KEYWORDS (page unavailable) says eRNAs contribute to gene control by stabilizing enhancer–promoter looping, supporting their role in linking enhancers and promoters. It also describes several other mechanisms, so it does not establish promoter modulation as their central role. Our copy does not give the claimed length of <2 kb. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Sense transcripts of NATs can be imprinted, polyadenylated, and spliced, but this may be less common than conventional sense and protein-coding pairs.

“In the same manner, their sense transcripts can be imprinted, polyadenylated, and spliced; however, this event might become less common than the conventional sense and protein-coding pairs [65].”

• cites [65] He, 2008, The Antisense Transcriptomes of Human Cells, Science sourcePartly supported

  The supplied passage on imprinted genes (section labeled Abstract; page unavailable) notes examples of antisense transcripts associated with imprinted genes. The splicing passage reports that about 1% of antisense fragments, versus more than 20% of sense fragments, showed a spliced pattern. Neither passage establishes that the sense transcripts of NATs are polyadenylated or that the claimed features are less common than in conventional sense protein-coding pairs. (LLM, conf=0.79)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

In a mammalian genome, the distribution of CpG dinucleotides is random, exhibiting regions of low and high density, known as CpG islands.

“In a mammalian genome, the distribution of CpG dinucleotides is random, exhibiting regions of low and high density, known as CpG islands [52].”

• cites [52] Flores, 2013, The role of methylation of DNA in environmental adaptation, Integr. Comp. Biol. sourcePartly supported

  The ‘DNA methylation increases mutability’ section reports patterns of CpG depletion at genomic loci, including in humans, which supports variation in CpG density. Our copy does not say that CpGs are randomly distributed in mammalian genomes or identify high-density regions as CpG islands; searches for those terms found no such passage. No page number was provided for the passage. (LLM, conf=0.76)

  Experimental — accuracy not yet measured

May combine two claims.

circRNA biogenesis is described as back-splicing in the post-transcriptional stage, forming a loop and serving as a bridge between mRNA and ncRNAs, modulating RNA transcription and protein translation or function.

“circRNA biogenesis has been described as back-splicing in the post-transcriptional stage, forming a loop and serving as a bridge between the mRNA and the ncRNAs, modulating RNA transcription and protein translation or function [74], in some cases, by sponging miRNAs exported post-transcriptionally in trans.”

• cites [74] Gu, A., Jaijyan, D.K., Yang, S., Zeng, M., Pei, S., and Zhu, H. (2023). Functions of circular RNA in human diseases and illnesses. Non-Coding RNA, 9. sourceSupported

May combine two claims.

Post-translational modifications in the amino acids of histone tails are recognized as the histone code, which can affect the accessibility of different proteins to DNA.

“Post-translational modifications in the amino acids of the histone tails are recognized as the histone code, which can affect the accessibility of different proteins to the DNA.”

• cites [55] Melamed, P., Yosefzon, Y., David, C., Tsukerman, A., and Pnueli, L. (2018). TET Enzymes, variants, and differential effects on function. Front. Cell Dev. Biol., 6. sourceCould not verify

  The section on TET enzymes and DNA hydroxymethylation says that modification of DNA can change which proteins bind, but it does not address modifications of histone tails or define a histone code. Searches for those terms and for histone modifications affecting protein access to DNA found no passage supporting the attributed claim. No page number is available in our copy. (LLM, conf=0.74)

  Experimental — accuracy not yet measured

May combine two claims.

circRNAs are a recently described, not fully characterized type of exonic ncRNAs covalently bonded from 5′ to 3′ sticky ends in a circle and commonly found in mammals.

“A recently described and not fully characterized type of exonic ncRNAs are covalently bonded from the 5′ to 3′ sticky ends in the shape of a circle, which is why they have been named circular RNAs (circRNAs) and are very commonly found in mammals.”

• cites [73] Zeng, X., Yuan, X., Cai, Q., Tang, C., and Gao, J. (2021). Circular RNA as an epigenetic regulator in chronic liver diseases. Cells, 10. sourcePartly supported

  The Introduction (page not provided) identifies circRNAs as non-coding RNAs with a covalently closed loop, generated from pre-mRNA by back-splicing. It does not describe them as specifically exonic, say that 5′ and 3′ sticky ends bond together, or establish that they are very common in mammals. Its discussion of unclear mechanisms concerns circRNAs in chronic liver diseases, not the characterization of circRNAs generally. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

May combine two claims.

miRNAs are derived from transcripts, intronic and intergenic sequences, form a unique hairpin structure processed into mature form, and mediate gene silencing at the post-transcriptional level by coupling to an RNA-induced silencing complex in the cytoplasm.

“This type of ncRNA is derived from transcripts, intronic and intergenic sequences, that form a unique hairpin structure to be processed into their mature form, which allows them to mediate gene silencing at the post-transcriptional level by coupling to an RNA-induced silencing complex in the cytoplasm.”

• cites [53] Kim, 2021, Multi-omics integration Strategies for animal Epigenetic studies, Anim. Biosci. sourcePartly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured
• cites [61] Winkle, 2021, Noncoding RNA therapeutics—Challenges and potential solutions, Nat. Rev. Drug Discov. sourcePartly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

piRNAs are 21-35 nucleotides long, longer than miRNAs, and can repress complementary transposons.

“piRNAs are somehow longer than miRNAs, being 21–35 nucleotides long, and can repress complementary transposons [70].”

• cites [70] Zhang, 2011, A k-mer scheme to predict piRNAs and characterize locust piRNAs, Bioinformatics sourcePartly supported

  The Introduction (page unavailable) says piRNAs are slightly longer than miRNAs, but gives their general length as 25–32 nt, not 21–35 nt. Results §3.6 (page unavailable) reports matches between predicted locust piRNAs and transposons; it does not show that those piRNAs repress complementary transposons. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

The generally accepted concept of epigenetics specifies mitotically and/or meiotically heritance and one that does not entail a change in genomic DNA.

“the generally accepted concept has obtained a more accurate definition as specifying mitotically and/or meiotically heritance and one that does not entail a change in genomic DNA.”

• cites [29] Goldberg, 2007, Epigenetics: A landscape takes shape, Cell sourcePartly supported

  The definition passage (section labeled Abstract; page unavailable) supports the claim that epigenetic changes do not alter the underlying DNA sequence. It describes those changes as potentially stable and *ideally* heritable, however, rather than requiring mitotic or meiotic inheritance as the citing sentence states. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

circRNAs have a key role in the epigenetic mediation of gene expression at both transcriptional and post-transcriptional levels, with a demonstrated function in liver diseases and homeostasis.

“circRNAs have a key role in the epigenetic mediation of gene expression at both transcriptional and post-transcriptional levels with a demonstrated function in liver diseases and homeostasis [73].”

• cites [73] Zeng, X., Yuan, X., Cai, Q., Tang, C., and Gao, J. (2021). Circular RNA as an epigenetic regulator in chronic liver diseases. Cells, 10. sourcePartly supported

  The Introduction describes circRNAs regulating target-gene expression through miRNA sponging, and the Introduction and Conclusions describe their roles in liver homeostasis and chronic liver diseases. However, the passage explicitly attributing regulation at both transcriptional and post-transcriptional levels concerns lncRNAs, not circRNAs; our copy does not establish both levels for circRNAs. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

NATs are categorized into two groups: one complementary in situ with its sense counterpart partially or completely, and one non-overlapping with the sense transcript but complementary to DNA at specific gene boundaries.

“Initially, they have been categorized within two different groups: On the one hand, there is the NAT group, which is complementary in situ with its sense counterpart, partially or completely. The second group is non-overlapping with the sense transcript, but still complementary to the DNA at specific gene boundaries.”

• cites [65] He, 2008, The Antisense Transcriptomes of Human Cells, Science sourcePartly supported

  The passages labeled Abstract (page unavailable) report antisense tags in exons and near gene promoters and terminators, supporting the claim’s general distinction between transcribed regions and gene boundaries. They do not classify NATs into the two stated groups or establish that boundary-associated antisense transcripts do not overlap their sense counterparts. The paper’s three S, AS, and SAS classes categorize genes by tag ratios, not NATs by overlap. (LLM, conf=0.82)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

lncRNAs can be bidirectional and can come from intronic or intergenic sequences, or from disruption of open reading frames or chromosomal rearrangements.

“These lncRNAs can be bidirectional, and they can come from intronic or intergenic sequences. They can also be derived from the disruption of open reading frames or chromosomal rearrangements.”

• cites [53] Kim, 2021, Multi-omics integration Strategies for animal Epigenetic studies, Anim. Biosci. sourceSupported
• cites [61] Winkle, 2021, Noncoding RNA therapeutics—Challenges and potential solutions, Nat. Rev. Drug Discov. sourcePartly supported

  The Introduction (page unavailable) describes lncRNAs transcribed antisense to coding genes, and the References list a study of large intergenic noncoding RNAs. These passages support some variation in lncRNA location or transcription direction, but they do not establish the claimed bidirectionality or derivation from intronic sequences, disrupted open reading frames, or chromosomal rearrangements. (LLM, conf=0.74)

  Experimental — accuracy not yet measured

May combine two claims.

circRNAs are associated with immune responses and dysregulation in virus-infected cells and tumorigenesis, as well as in the behavior and accumulation of neural cells and tissues through aging.

“They have been associated with immune responses and dysregulation in virus-infected cells and tumorigenesis, as well as in the behavior and accumulation of neural cells and tissues through aging.”

• cites [74] Gu, A., Jaijyan, D.K., Yang, S., Zeng, M., Pei, S., and Zhu, H. (2023). Functions of circular RNA in human diseases and illnesses. Non-Coding RNA, 9. sourcePartly supported

  Sections 3.4 and 4.1–4.3 link circRNAs to immune responses, viral infection and altered expression in infected cells; the Introduction links them to tumorigenesis. Section 3.7 describes circRNA enrichment in brain structures and a role in neural function, but the passages do not establish that circRNAs accumulate in neural cells or tissues through aging. Page numbers are unavailable in our copy. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

It is estimated that 30% of human genes are regulated by miRNAs.

“Very interestingly, it is estimated that 30% of human genes are regulated by miRNAs [53,61].”

• cites [53] Kim, 2021, Multi-omics integration Strategies for animal Epigenetic studies, Anim. Biosci. sourcePartly supported

  The RNA interference section says miRNAs regulate many genes and describes a study of potential targets among 13,000 human genes. It does not estimate that miRNAs regulate 30% of human genes; its 50% figure concerns chromosomal regions, not genes. No page number is available in our copy. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites [61] Winkle, 2021, Noncoding RNA therapeutics—Challenges and potential solutions, Nat. Rev. Drug Discov. sourcePartly supported

  The Introduction (page unavailable) describes miRNAs as gene regulators. The hurdle of specificity (page unavailable) reports that one miRNA cluster can affect about 14% of the transcriptome in leukaemic cells, but it does not support the estimate that miRNAs regulate 30% of human genes. (LLM, conf=0.83)

  Experimental — accuracy not yet measured

May combine two claims.

Specific expression profiles point toward increasing levels of monomethylation in the case of H3 and repressing levels of H3K4me3 marks.

“Specific expression profiles have pointed towards increasing levels of monomethylation in the case of H3 and repressing levels of H3K4me3 marks.”

• cites [77] Bose, 2017, RNA Binding to CBP Stimulates Histone Acetylation and Transcription, Cell sourceCould not verify

  The STAR Methods section lists H3K4me1 and H3K4me3 datasets, but does not report increasing H3 monomethylation or repression of H3K4me3. The Results passages instead describe changes in histone acetylation. Searches for H3K4me1, H3K4me3, monomethylation, and expression profiles found no passage supporting the attributed claim; page numbers were unavailable in our copy. (LLM, conf=0.76)

  Experimental — accuracy not yet measured
• cites [78] Ye, 2020, Enhancer RNA: Biogenesis, function, and regulation, Essays Biochem. sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

piRNAs are part of the sncRNAs and are involved at transcriptional and post-transcriptional levels.

“First discovered in the Drosophila melanogaster germ line, piRNAs are part of the sncRNAs, which are involved at transcriptional and post-transcriptional levels [66].”

• cites [66] Huang, S., Yoshitake, K., and Asakawa, S. (2021). A Review of Discovery Profiling of PIWI-Interacting RNAs and Their Diverse Functions in Metazoans. Int. J. Mol. Sci., 22. sourceSupported

May combine two claims.

Histone codes are involved in cell differentiation, cell mitosis, the repair of DNA damage, and X chromatin inactivation.

“The histone codes are involved in cell differentiation, cell mitosis, the repair of DNA damage, and X chromatin inactivation, and mediate transcriptional inhibition or activation, leading to many biological effects [55].”

• cites [55] Melamed, P., Yosefzon, Y., David, C., Tsukerman, A., and Pnueli, L. (2018). TET Enzymes, variants, and differential effects on function. Front. Cell Dev. Biol., 6. sourceCould not verify

  The sections on TET enzymes and on different isoforms discuss DNA hydroxymethylation, differentiation, and TET1-mediated transcriptional repression; the latter also mentions an H3K27 histone mark. Searches for “histone code,” mitosis, DNA-damage repair, and X-chromatin inactivation found no passage attributing the listed functions to histone codes. The cited paper therefore does not verify this claim. (LLM, conf=0.73)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Mature miRNAs are RNA molecules around 20 nucleotides in length, widely conserved among species, with diverse functions, and involved in regulation of gene expression in multicellular eukaryotes and some unicellular eukaryotes.

“Mature miRNAs are RNA molecules of around 20 nucleotides in length that are widely conserved among species with diverse functions and involved in the regulation of gene expression in multicellular eukaryotes and some unicellular eukaryotes.”

• cites [53] Kim, 2021, Multi-omics integration Strategies for animal Epigenetic studies, Anim. Biosci. sourcePartly supported

  The RNA interference section describes miRNAs as evolutionarily conserved, approximately 24 nucleotides long, and regulators of hundreds of genes through effects on mRNA. That broadly supports the claimed size and gene-regulatory role, but the section does not say that miRNAs function in some unicellular eukaryotes. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [61] Winkle, 2021, Noncoding RNA therapeutics—Challenges and potential solutions, Nat. Rev. Drug Discov. sourcePartly supported

  The Introduction describes miRNAs as highly conserved, 17–25-nucleotide RNAs that regulate genes, and the specificity section describes their ability to target multiple mRNAs. The cited passages do not establish that this regulation occurs in some unicellular eukaryotes; the claim's organismal scope is therefore not fully supported. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

More than 2000 transcription factors, and 1600 in humans, have been characterized in cells.

“Nevertheless, on the other hand, since the first discovery of the Retinoblastoma tumor suppressor gene 1 (RB1), a transcriptional factor with demethylation capacities, if we consider that to date, more than 2000 transcription factors and 1600 in humans [60] have been characterized in cells, only a small number of them have been related with demethylation or methylation.”

• cites [60] Lambert, 2018, The human transcription factors, Cell sourcePartly supported

  The human TF repertoire section reports 1,639 known or likely human transcription factors, supporting the approximate figure of 1,600. It does not establish the claim of more than 2,000 transcription factors overall, and its 'known or likely' tally does not mean every factor has been characterized in cells. No page number is available in our copy. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

DNA methylation is involved in phenotypic inheritance in single-celled organisms, as well as in transgenerational inheritance in multicellular organisms.

“DNA methylation is involved in phenotypic inheritance in single-celled organisms, as well as in transgenerational inheritance in multicellular organisms.”

• cites [52] Flores, 2013, The role of methylation of DNA in environmental adaptation, Integr. Comp. Biol. sourcePartly supported

  The section “Evidence for transgenerational inheritance of DNA methylation” describes methylation-dependent inherited stress responses in plants, supporting the multicellular-organism part of the claim. The passages found do not address phenotypic inheritance in single-celled organisms, so that part is unsupported by our copy. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

May combine two claims.

Methylation of the gene body appears to contribute to elongation during transcription, regulation of alternative splicing, and regulation of non-coding RNAs.

“However, the methylation of the gene body appears to contribute to elongation during transcription, the regulation of alternative splicing, and the regulation of non-coding RNAs.”

• cites [53] Kim, 2021, Multi-omics integration Strategies for animal Epigenetic studies, Anim. Biosci. sourcePartly supported

  The DNA methylation section (page unavailable) says methylation in genes may stimulate transcriptional elongation and splicing, supporting those parts of the claim. It does not specify alternative splicing or say that gene-body methylation regulates non-coding RNAs. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

piRNAs have been incorrectly categorized only in animals; the correct definition is within the metazoans group.

“piRNAs regulate epigenetic mechanisms involved in germ cell development, and inaccurately, this kind of ncRNA has been only categorized in animals, while the correct definition is within the metazoans group [68,69].”

• cites [68] Zhang, 2023, The epigenetic regulatory mechanism of PIWI/piRNAs in human cancers, Mol. Cancer sourceCould not verify

  The Introduction’s ‘Overview of piRNAs’ describes piRNAs in Drosophila, invertebrates, and vertebrates, but does not say that categorizing them in animals is incorrect or that ‘metazoans’ is the correct definition. Searches for those classification terms found no passage addressing the claimed correction. (LLM, conf=0.74)

  Experimental — accuracy not yet measured
• cites [69] Gainetdinov, 2018, PIWI-interacting RNAs: Small RNAs with big functions, Nat. Rev. Genet.Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

DNA methylation is regulated by DNA methyltransferases (DNMTs), which catalyze transfer of a methyl group from S-adenosylmethionine (SAM) to cytokines.

“Given its reversible nature, DNA methylation is regulated by DNA methyltransferases (DNMTs), which catalyze the transfer of a methyl group from a donor group called S-adenosylmethionine (SAM) to cytokines.”

• cites [55] Melamed, P., Yosefzon, Y., David, C., Tsukerman, A., and Pnueli, L. (2018). TET Enzymes, variants, and differential effects on function. Front. Cell Dev. Biol., 6. sourcePartly supported

  The section “The TET enzymes, DNA hydroxymethylation, and demethylation” describes DNMT1 acting at hemimethylated DNA sites, supporting the DNMT connection to methylation. It does not describe SAM as the methyl donor or the claimed transfer reaction. The paper discusses cytosines, not cytokines, as the DNA bases involved. (LLM, conf=0.82)

  Experimental — accuracy not yet measured

May combine two claims.

Enhancers are related to p300/CBP, as coactivators have been found as a component in the chromatin.

“In this sense, enhancers have been related to p300/CBP, as coactivators have been found as a component in the chromatin.”

• cites [77] Bose, 2017, RNA Binding to CBP Stimulates Histone Acetylation and Transcription, Cell sourceSupported
• cites [78] Ye, 2020, Enhancer RNA: Biogenesis, function, and regulation, Essays Biochem. sourceNot checked — no full text of the source

May combine two claims.

ncRNAs play a major regulatory role in the epigenetic transgenerational transmission of the effects of reprotoxicants on the development and differentiation of germ cells, and subsequently in reducing mammalian fertility as a result of exposure to environmental pollutants during early development.

“ncRNAs have been studied to play a major regulatory role in the epigenetic transgenerational transmission of the effects of reprotoxicants on the development and differentiation of germ cells, and subsequently, in reducing mammalian fertility as a result of exposure to environmental pollutants during early development [103] (see the review by Larriba y del Mazo 2016).”

• cites [103] Larriba, E., and del Mazo, J. (2016). Role of Non-Coding RNAs in the Transgenerational Epigenetic Transmission of the Effects of Reprotoxicants. Int. J. Mol. Sci., 17. sourcePartly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

May combine two claims.

When bisphenol A (BPA) is added to a mother's diet, the children had lower CpG methylation at the Avy allele, as well as higher rates of a yellow coat color, obesity, and diabetes.

“When bisphenol A (BPA), a substance often used in the production of polycarbonate plastics, is added to a mother’s diet, the children had lower CpG methylation at the Avy allele, as well as higher rates of a yellow coat color, obesity, and diabetes [104].”

• cites [104] Dolinoy, 2007, Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development, Proc. Natl. Acad. Sci. USA sourcePartly supported

  The Results (page unavailable) report lower Avy CpG methylation and a higher proportion of yellow-coated offspring after maternal dietary BPA exposure. The paper’s background links expression of the Avy allele to obesity and diabetes, but the study does not report higher rates of either condition in the BPA-exposed offspring. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Comparative epigenomics links evolutionary phylogenesis and epigenetic indicators to find traits related to life span.

“A recently emerging discipline called comparative epigenomics links evolutionaryphylogenesis and epigenetic indicators to find traits related to life span [85].”

• cites [85] Haghani, 2023, DNA methylation networks underlying mammalian traits, Science sourceSupported

May combine two claims.

Positive regulation of miRNA-510 and negative regulation of miRNA-342 and 191 contribute to the development of diabetes.

“It has also been reported that there is positive regulation of miRNA-510, as well as negative regulation of miRNA-342 and 191, which contribute to the development of the disease [90,91].”

• cites [90] Mazzone, 2019, The emerging role of epigenetics in human autoimmune disorders, Clin. Epigenetics sourcePartly supported

  The Type 1 diabetes (T1D) section reports upregulated miR-510 and downregulated miR-342 and miR-191 in T1D. It describes these expression changes as associated with T1D, but does not establish that they contribute to the disease’s development. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [91] Shanmugam, 2012, Role of Epigenetics in Inflammation-Associated diseases, Epigenetics: Development and Disease sourceNot checked — no full text of the source

May combine two claims.

At the TNF-α locus, epigenetic changes lead to a change in chromatin structure from heterochromatin to euchromatin, and methylation marks are replenished mediated by the MLL enzyme.

“At its locus, it leads to a change in chromatin structure (from heterochromatin to euchromatin), and methylation marks have also been replenished at this level mediated by the mixed lineage leukemia (MLL) enzyme.”

• cites [86] Stylianou, 2018, Epigenetics of chronic inflammatory diseases, J. Inflamm. Res. sourcePartly supported

  The sections on chromatin architecture and histone modifications (page unavailable) describe chromatin reorganization and methylation marks associated with euchromatin and heterochromatin. They do not establish a heterochromatin-to-euchromatin change at the TNF-α locus or say that MLL replenishes methylation marks there. (LLM, conf=0.78)

  Experimental — accuracy not yet measured
• cites [87] Lacagnina, 2019, The Developmental Origins of Health and Disease (DOHAD), Am. J. Lifestyle Med. sourcePartly supported

  The Objectives section describes epigenetics as involving conformational changes in chromatin, and the paper’s opening section discusses methylation as a genomic modification; page numbers are unavailable in our copy. Neither passage establishes a heterochromatin-to-euchromatin transition at the TNF-α locus or says that MLL replenishes methylation marks (searched: TNF, heterochromatin, euchromatin, MLL). (LLM, conf=0.77)

  Experimental — accuracy not yet measured

May combine two claims.

TNF-α undergoes epigenetic modifications at DNA methylation in its promoter (hypermethylation and hypomethylation) to regulate its expression or at histone modifications due to acetylation orchestrated by ATF2 and CBP.

“As an example of the above, it has been described that TNF-α undergoes epigenetic modifications at the level of DNA methylation in its promoter (hypermethylation and hypomethylation) to regulate its expression or at the level of histone modifications due to acetylation orchestrated by the enzymes activating transcription factor 2, ATF2, and the CREB binding protein (CBP).”

• cites [86] Stylianou, 2018, Epigenetics of chronic inflammatory diseases, J. Inflamm. Res. sourceCould not verify

  The DNA modifications and Histone modifications sections describe methylation and acetylation as general mechanisms of gene regulation, but do not link them to TNF-α. Searches for TNF-α promoter methylation and for ATF2/CBP-mediated acetylation found no passage addressing the specific example attributed to this paper; page numbers were not available in our copy. (LLM, conf=0.76)

  Experimental — accuracy not yet measured
• cites [87] Lacagnina, 2019, The Developmental Origins of Health and Disease (DOHAD), Am. J. Lifestyle Med. sourceCould not verify

  The DOHaD section discusses methylation and other genome modifications in general, but does not address TNF-α. Searches for TNF-α promoter methylation, histone acetylation, ATF2, and CBP found no passage supporting the specific mechanisms attributed to this paper; page numbers are unavailable in our copy. (LLM, conf=0.76)

  Experimental — accuracy not yet measured

May combine two claims.

Such molecules are constitutively produced by different cells during chronic inflammatory conditions, leading to the development of lung and neurodegenerative diseases and cancer.

“Such molecules are constitutively produced by different cells during chronic inflammatory conditions, which in turn leads to the development of lung and neurodegenerative diseases and cancer [86].”

• cites [86] Stylianou, 2018, Epigenetics of chronic inflammatory diseases, J. Inflamm. Res. sourcePartly supported

  In “Physiological and pathological inflammation > Initiation” (page not provided), the paper describes cytokine-mediated inflammatory loops involving immune and resident cells. “Alzheimer’s disease > Molecular and clinical features” (page not provided) links failure to resolve brain inflammation with Alzheimer’s pathology. Our copy does not support the stronger claim that these molecules are constitutively produced or that their production leads to lung disease and cancer. (LLM, conf=0.82)

  Experimental — accuracy not yet measured

May combine two claims.

Models of nutritional restriction and uteroplacental insufficiency suggest that the gestational environment influences the postnatal phenotype, which may increase susceptibility to childhood obesity through metabolic reprogramming.

“Other investigations with models of nutritional restriction and uteroplacental insufficiency suggest that the gestational environment influences the postnatal phenotype, which may increase susceptibility to childhood obesity through metabolic reprogramming [95].”

• cites [95] Lacagnina, 2019, Distinct hippocampal engrams control extinction and relapse of fear memory, Nat. Neurosci. sourceCould not verify

  The Results passages describe hippocampal neurons involved in fear conditioning and extinction, not gestational influences on postnatal phenotype. Searches for nutritional restriction, uteroplacental insufficiency, childhood obesity, and metabolic reprogramming found no passage addressing the claim. (LLM, conf=0.78)

  Experimental — accuracy not yet measured

May combine two claims.

miRNAs target the BACE1 protein that regulates the production of amyloid beta platelets, Aβ, which when accumulated contribute to neuroinflammation and progression of Alzheimer's disease.

“Likewise, it has been reported that there are miRNAs that target the BACE1 protein that regulates the production of amyloid beta platelets, Aβ, which, when accumulated, contribute to the neuroinflammation and progression of this disease [86,87,88].”

• cites [86] Stylianou, 2018, Epigenetics of chronic inflammatory diseases, J. Inflamm. Res. sourcePartly supported

  The Alzheimer’s disease > MicroRNAs section says miRNAs target mRNAs for proteins involved in Aβ processing, including BACE1, which regulates Aβ production. The Molecular and clinical features section says accumulated Aβ plaques contribute to neuroinflammation and disease progression. The citing sentence is imprecise: the paper describes targeting BACE1 mRNA, not the protein directly, and calls the deposits plaques, not platelets. (LLM, conf=0.85)

  Experimental — accuracy not yet measured
• cites [87] Lacagnina, 2019, The Developmental Origins of Health and Disease (DOHAD), Am. J. Lifestyle Med. sourceCould not verify

  The Objectives passages discuss early-life epigenetic changes and metabolic disease, not Alzheimer’s disease. Searches of our copy for BACE1, miRNAs, amyloid beta, and neuroinflammation returned no passage addressing the attributed mechanism. (LLM, conf=0.74)

  Experimental — accuracy not yet measured
• cites [88] Maruyama, R., Choudhury, S., Kowalczyk, A., Bessarabova, M., Beresford-Smith, B., Conway, T., Kaspi, A., Wu, Z.J., Nikolskaya, T., and Merino, V.F. (2011). Epigenetic regulation of cell Type–Specific expression patterns in the human mammary epithelium. PLOS Genet., 7. sourceCould not verify

  The Results passage on gene expression and histone modification patterns and the Discussion passage on K27-regulated transcription factors concern human mammary epithelial cells. Searches for BACE1, miRNAs, amyloid beta, neuroinflammation, and Alzheimer’s disease found no passage in our copy addressing the attributed claim. (LLM, conf=0.78)

  Experimental — accuracy not yet measured

May combine two claims.

In diabetes, increased levels of histone methylations have been identified in the promoter of CLT4, a gene highly susceptible to type 1 diabetes, and correlated with the activation of T cells.

“In other diseases such as diabetes, increased levels of histone methylations have been identified in the promoter of CLT4, a gene highly susceptible to type 1 diabetes that has been correlated with the activation of T cells.”

• cites [90] Mazzone, 2019, The emerging role of epigenetics in human autoimmune disorders, Clin. Epigenetics sourceSupported
• cites [91] Shanmugam, 2012, Role of Epigenetics in Inflammation-Associated diseases, Epigenetics: Development and Disease sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

ncRNAs could interact with mRNA methylation through a different mechanism.

“Through a different mechanism, ncRNAs could interact with mRNA methylation [79].”

• cites [79] Romano, G., Veneziano, D., Nigita, G., and Nana-Sinkam, S.P. (2018). RNA Methylation in ncRNA: Classes, Detection, and Molecular Associations. Front. Genet., 9. sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

Chromatin remodelings also comprise ATP-dependent enzymes.

“However, it has been well established that chromatin remodelings also comprise ATP-dependent enzymes [83].”

• cites [83] Ho, 2010, Chromatin remodelling during development, Nature sourceSupported

May combine two claims.

Environmental factors can influence epigenetic mechanisms, and deregulation at any point can lead to different diseases.

“However, it is necessary to keep in mind that environmental factors can influence epigenetic mechanisms and that at any point of deregulation, different diseases can develop [94].”

• cites [94] Roshan, J., and Rougeulle, C. (2018). Developmental epigenetics: Phenotype and the flexible epigenome. Front. Cell Dev. Biol., 6. sourcePartly supported

  The Fetal programming section (page unavailable) links early-life exposures to later obesity, metabolic disease, and mental-health risks, and describes epigenetic dysregulation as a potential mechanism. It does not establish that deregulation at any point causes disease; it says the epigenetic mechanism remains unproven and that vulnerability may depend on developmental timing. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

At the biochemical level, the NuRD complex, with nucleosome remodeling and deacetylase roles, is epigenetically involved in gene regulation, with DNA fixed via binding where damage occurs on multiple loci spots.

“At the biochemical level, the NuRD complex, with nucleosome remodeling and deacetylase roles, is epigenetically involved in gene regulation, with DNA fixed via binding where the damage occurs on multiple loci spots [110].”

• cites [110] Basta, 2015, The nucleosome remodeling and deacetylase complex in development and disease, Transl. Res. (Online) sourcePartly supported

  The NuRD Biochemistry section describes NuRD’s nucleosome-remodeling and deacetylase activities and its role in regulating gene expression. The Cancer and Ageing section reports a role in DNA-damage response and describes recruitment to damage sites as a potential mechanism. It does not establish that DNA is repaired through binding at multiple loci, as the citing sentence implies. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

BRCA1 and USP44 have been reported to be of great interest in breast cancer, since BRCA1 is a tumor suppressor and USP44 still has unknown oncogenic potential.

“For instance, BRCA1 and USP44 have been reported to be of great interest in breast cancer, since the first protein is a tumor suppressor, and the second one still has an unknown oncogenic potential.”

• cites [52] Flores, 2013, The role of methylation of DNA in environmental adaptation, Integr. Comp. Biol. sourceCould not verify

  The passages from “The genomic functional roles of DNA methylation” and “Remarks and future work” discuss methylation and environmental adaptation, not the roles of BRCA1 or USP44 in breast cancer. Searches for both proteins and USP44’s oncogenic potential found no passage addressing the claim in our copy. (LLM, conf=0.76)

  Experimental — accuracy not yet measured
• cites [106] Orsini, A., Diquigiovanni, C., and Bonora, E. (2023). Omics Technologies improving breast cancer research and diagnostics. Int. J. Mol. Sci., 24. sourcePartly supported

  Section 3.1 (page unavailable) discusses BRCA1 silencing in sporadic breast cancer, supporting BRCA1's relevance to the disease. It does not identify BRCA1 as a tumor suppressor, and searches for USP44 and its oncogenic potential found no passage addressing either point. (LLM, conf=0.82)

  Experimental — accuracy not yet measured

May combine two claims.

Omics data often lack certain values, and in studies on omics data, individuals are generally represented in some, but not all, omics layers.

“However, omics data often lack certain values, and in studies on omics data, individuals are generally represented in some, but not all, omics layers [105].”

• cites [105] Song, M., Greenbaum, J., Luttrell, J., Zhou, W., Wu, C., Shen, H., Gong, P., Zhang, C., and Deng, H.W. (2020). A review of Integrative Imputation for Multi-Omics Datasets. Front. Genet., 11. sourceSupported

Probably not a substantial claim: may not pass S4 (based).

There is a relatively small amount of information regarding studies that link ncRNAs and methylation or chromatin remodeling.

“there is a relatively small amount of information regarding studies that link ncRNAs and methylation or chromatin remodeling (Figure 2).”

Classified as probably not a substantial claim.

There is a relevant gap of knowledge in interrelating more than one single epigenetic mechanism.

“Furthermore, there is a relevant gap of knowledge in terms of interrelating more than one single mechanism; for instance, there is a relatively small amount of information regarding studies that link ncRNAs and methylation or chromatin remodeling (Figure 2).”

May combine two claims.

In 2020, the uninterrupted increase in publications over the previous three decades was interrupted, with only a few more than 40 publications per day.

“However, in the recent year of 2020, exactly three decades of undiminished publications were interrupted with only a few more than 40 publications per day.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Waddington defined epigenetics as the developmental process that mediates between genotype and phenotype.

“or through the complex “developmental process that mediates between genotype and phenotype” [31]”

• cites [31] Waddington, 1942, The epigenotype, Int. J. Epidemiol. sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Waddington defined epigenetics as the study of all the events that lead to the development of the genetic program of development.

“he stated it as “the study of all the events that lead to the development of the genetic program of development” [30]”

• cites [30] Waddington, C.H. (1939). An Introduction to Modern Genetics, The Macmillan Company. sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The term epigenetics was coined and defined by Conrad H. Waddington in the late 1930s.

“The term epigenetics was coined and also defined by Conrad H. Waddington in the late 1930s.”

• cites [30] Waddington, C.H. (1939). An Introduction to Modern Genetics, The Macmillan Company. sourceNot checked — no full text of the source

May combine two claims.

The yellow mother had more yellow pups and the mottled mother had more mottled pups; the epigenetic marks introduced enabled segregation of their characters.

“The yellow mother had more yellow pups and the mottled mother had more mottled pups; the epigenetic marks introduced enabled the segregation of their characters.”

• cites [39] Russo, V., Martienssen, R.A., and Riggs, A.D. (1996). Epigenetic Mechanisms of Gene Regulation, Cold Spring Harbor Laboratory Press. Available online: http://ci.nii.ac.jp/ncid/BA29742198.Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

Epigenetics can be defined as a post-replication event due to alterations in gene expression patterns in a single cell lineage absent from changes in the genomic DNA sequence.

“The most widely accepted theory is that epigenetics can be defined as a post-replication event due to alterations in the gene expression patterns in a single cell lineage absent from changes in the genomic DNA sequence.”

Probably not a substantial claim: may not pass S3 (load-bearing).

A considerable amount of the transcriptome consists of endogenous transcripts with inverse orientation serving as a template of RNA polymerase II.

“During its discovery, it was brought to our attention the fact that a considerable amount of the transcriptome was endogenous transcripts with inverse orientation serving as a template of RNA polymerase II [64].”

• cites [64] Goodrich, 2006, Non-coding-RNA regulators of RNA polymerase II transcription, Nat. Rev. Mol. Cell Biol. sourceNot checked — no full text of the source

May combine two claims.

The phenomenon of inheritance of acquired traits and segregation was first discovered in yeast, fruit flies, and plants, and was described convincingly in mammals in 1999 by Emma Withelaw and collaborators using a genomically almost identical strain of mice with a coat color difference from mottled to yellow.

“This phenomenon was first discovered in yeast, fruit flies, and plants, and was described convincingly in mammals in 1999 by Emma Withelaw and her collaborators using a genomically almost identical strain of mice with a slight difference in coat color from mottled to yellow.”

• cites [38] Balter, 2000, Was Lamarck Just a Little Bit Right?, Science sourceNot checked — no full text of the source

May combine two claims.

Natural antisense transcripts cover a broad and ubiquitous spectrum and have complementary sequences that indirectly interact with targets such as DNA methyltransferases, histone acetylases, and deacetylases.

“From the major regulatory epigenetic mechanisms, natural antisense transcripts (NATs) cover a broad and ubiquitous spectrum, besides complementary sequences indirectly interacting with other targets like DNA methyltransferases, histone acetylases, and deacetylases [62].”

• cites [62] Su, 2010, Natural antisense transcripts regulate gene expression in an epigenetic manner, Biochem. Biophys. Res. Commun. sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

NATs can either overlap or not with mature conventional sense sequences.

“NATs can either overlap or not with mature conventional sense sequences [62].”

• cites [62] Su, 2010, Natural antisense transcripts regulate gene expression in an epigenetic manner, Biochem. Biophys. Res. Commun. sourceNot checked — no full text of the source

May combine two claims.

Diverse types of ncRNAs, divergently expressed, overlap with protein-coding genes and are widespread in mammalian genomes.

“There are diverse types of ncRNAs, divergently expressed, that overlap with protein-coding genes and are also widespread in mammalian genomes.”

• cites [64] Goodrich, 2006, Non-coding-RNA regulators of RNA polymerase II transcription, Nat. Rev. Mol. Cell Biol. sourceNot checked — no full text of the source

May combine two claims.

NATs' genomic structure enables regulation of their expression in cis, and they could also regulate expression in transposition depending on domain size.

“Their genomic structure enables the regulation of their expression in cis, but could also regulate expression in transposition, although it depends on how large the domain is.”

• cites [63] Williams, 1986, A mouse locus at which transcription from both DNA strands produces mRNAs complementary at their 3′ ends, Nature sourceNot checked — no full text of the source

May combine two claims.

The classical concept of transgenerational epigenetic inheritance has an effect until the F3 generation because if the event happened in the pregnant mother, it would affect the child and also their own germline.

“The classical concept of transgenerational epigenetic inheritance has an effect until the F3 generation due to the fact that if the event happened in the pregnant mother, it would affect the child, but also their own germline.”

May combine two claims.

NATs display conservation across the kingdoms of life and are involved in transcription or in ncRNA genesis.

“They display conservation all across the kingdoms of life, being involved in transcription or in ncRNA genesis.”

• cites [63] Williams, 1986, A mouse locus at which transcription from both DNA strands produces mRNAs complementary at their 3′ ends, Nature sourceNot checked — no full text of the source

May combine two claims.

Phenotypic changes can be environmentally induced and segregated across offspring from generation to generation.

“In this sense, phenotypic changes can be environmentally induced and segregated across offspring from generations to generations; particular studies have been centered on the effect of stress in a wide range of model organisms [59].”

• cites [59] Mirouze, 2011, Epigenetic contribution to stress adaptation in plants, Curr. Opin. Plant Biol. sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Epigenetic mechanisms are processes that can be reversible, in comparison with genetic mechanisms of gene modulation.

“Molecular functional roles can be modulated through various epigenetic mechanisms, which are processes that can be reversible, in comparison with genetic mechanisms of gene modulation.”

May combine two claims.

NATs can contribute to gene expression switching transcription and can act within protein complexes as a modular scaffold; in both functions they can rewire expression machinery.

“Either way, it could contribute to gene expression switching transcription, and also, it can act within protein/complexes as a modular scaffold; in both functions, it can rewire expression machinery [63].”

• cites [63] Williams, 1986, A mouse locus at which transcription from both DNA strands produces mRNAs complementary at their 3′ ends, Nature sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Lipid oxidation, toxicology, and epigenetics are understudied areas.

“For this aspect, lipid oxidation, toxicology, and epigenetics are understudied areas [121,122];”

• cites [121] Kuppusamy, 2015, Epigenetic Regulation in Environmental Chemical Carcinogenesis and its Applicability in Human Health Risk Assessment, Int. J. Toxicol. sourceNot checked — no full text of the source
• cites [122] Zaina, 2014, Atherosclerosis, cell biology and lipoproteins—Epigenetics and oxidation in atherosclerosis, Curr. Opin. Lipidol. sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

The low success rates in animal cloning of Euarchontoglires or other primates might be due to epigenetic mechanisms that act in every species that are evolutionarily closer to Homo sapiens.

“This might be due to epigenetic mechanisms that act in every species that are evolutionary closer to Homo sapiens.”

• AssumptionRests on an assumption: In animal models, particularly towards cloning Euarchontoglires or other primates, success rates are very low.

May combine two claims.

Epigenetic modification mechanisms act to modulate gene expression in different molecular processes of the cell, can be stochastic or induced by the environment, and are reversible and transmissible between generations of cells.

“Altogether, the epigenetic modification mechanisms described above act to modulate gene expression in different molecular processes of the cell, and these can be stochastic (determined during development by inherited genetic variants) or induced by the environment; they are also reversible and transmissible between generations of cells.”

• cites [84] Zhang, 2020, Epigenetics in health and disease, Epigenetics in Allergy and Autoimmunity sourceNot checked — no full text of the source