Cited by 2,700Epigenetics and DNA MethylationRNA modifications and cancerDNA and Nucleic Acid Chemistry

The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.

The Nuclear DNA Base 5-Hydroxymethylcytosine Is Present in Purkinje Neurons and the Brain

Open access

Kriaucionis, Skirmantas, Heintz, Nathaniel·2009·Science

DOI 10.1126/science.1169786PMC PMC3263819

Open this paper in CoChat — free account

Abstract

Despite the importance of epigenetic regulation in neurological disorders, little is known about neuronal chromatin. Cerebellar Purkinje neurons have large and euchromatic nuclei, whereas granule cell nuclei are small and have a more typical heterochromatin distribution. While comparing the abundance of 5-methylcytosine in Purkinje and granule cell nuclei, we detected the presence of an unusual DNA nucleotide. Using thin-layer chromatography, high-pressure liquid chromatography, and mass spectrometry, we identified the nucleotide as 5-hydroxymethyl-2'-deoxycytidine (hmdC). hmdC constitutes 0.6% of total nucleotides in Purkinje cells, 0.2% in granule cells, and is not present in cancer cell lines. hmdC is a constituent of nuclear DNA that is highly abundant in the brain, suggesting a role in epigenetic control of neuronal function.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1126/science.1169786

Cites

14 of 14 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

A translational profiling approach for the molecular characterization of CNS cell types
Heiman, M., Schaefer, A., Gong, S., Peterson, J. D., Day, M., Ramsey, K. E., Suárez-Fariñas, M., Schwarz, C., Stephan, D. A., Surmeier, D. J., et al. (2008) · Cell · doi:10.1016/j.cell.2008.10.028 · Cited by 1,134
Self-citation
Application of a translational profiling approach for the comparative analysis of CNS cell types
Doyle, J. P., Dougherty, J. D., Heiman, M., Schmidt, E. F., Stevens, T. R., Ma, G., Bupp, S., Shrestha, P., Shah, R. D., Doughty, M. L., et al. (2008) · Cell · doi:10.1016/j.cell.2008.10.029 · Cited by 912
Self-citation
Oxidative damage to methyl-CpG sequences inhibits the binding of the methyl-CpG binding domain (MBD) of methyl-CpG binding protein 2 (MeCP2)
Valinluck, V. (2004) · Nucleic Acids Research · doi:10.1093/nar/gkh739 · Cited by 756
The bases of the nucleic acids of some bacterial and animal viruses: the occurrence of 5-hydroxymethylcytosine
Wyatt, G. R., & Cohen, S. (1953) · Biochemical Journal · doi:10.1042/bj0550774 · Cited by 608
The Colorful History of Active DNA Demethylation
Ooi, S. K. T., & Bestor, T. H. (2008) · Cell · doi:10.1016/j.cell.2008.06.009 · Cited by 537
The presence of 5-hydroxymethylcytosine in animal deoxyribonucleic acid
Penn, N. W., SUWALSKI, R. T., O'Riley, C., Bojanowski, K., & Yura, R. (1972) · Biochemical Journal · doi:10.1042/bj1260781 · Cited by 280
Hypermodified bases in DNA
Gommers-Ampt, J., & Borst, P. (1995) · The FASEB Journal · doi:10.1096/fasebj.9.11.7649402 · Cited by 126
Solid phase synthesis and restriction endonuclease cleavage of oligodeoxynucleotides containing 5-(hydroxymethyl)-cytosine
Tardy-Planechaud, S. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.3.553 · Cited by 88
Oxidative damage to 5-methylcytosine in DNA
Zuo, S., Boorstein, R. J., & Teebor, G. W. (1995) · Nucleic Acids Research · doi:10.1093/nar/23.16.3239 · Cited by 87
Reaction of bisulfite with the 5-hydroxymethyl group in pyrimidines and in phage DNAs
Hayatsu, H., & Shiragami, M. (1979) · Biochemistry · doi:10.1021/bi00571a013 · Cited by 85

Flagged first, then by citations

Show all 14 references

Research works printed but not linked: 1

Ramsahoye B. H., Methods Mol. Biol. 200, 9 (2002).Medline

Sorted by citations

Items 301–400 of 1,015

Single-cell 5hmC sequencing reveals chromosome-wide cell-to-cell variability and enables lineage reconstruction
Mooijman, D., Dey, S. S., Boisset, J.-C., Crosetto, N., & van Oudenaarden, A. (2016) · Nature Biotechnology · doi:10.1038/nbt.3598 · Cited by 166
DNA hydroxymethylation controls cardiomyocyte gene expression in development and hypertrophy
Greco, C. M., Kunderfranco, P., Rubino, M., Larcher, V., Carullo, P., Anselmo, A., Kurz, K., Carell, T., Angius, A., Latronico, M. V. G., et al. (2016) · Nature Communications · doi:10.1038/ncomms12418 · Cited by 173
Epigenome Mapping in Normal and Disease States
Maunakea, A. K., Chepelev, I., & Zhao, K. (2010) · Circulation Research · doi:10.1161/circresaha.110.222463 · Cited by 165
Induced DNA demethylation by targeting Ten-Eleven Translocation 2 to the human ICAM-1 promoter
Chen, H., Kazemier, H. G., de Groote, M. L., Ruiters, M. H. J., Xu, G., & Rots, M. G. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt1019 · Cited by 164
Cell type specific transcriptomic differences in depression show similar patterns between males and females but implicate distinct cell types and genes
Maitra, M., Mitsuhashi, H., Rahimian, R., Chawla, A., Yang, J., Fiori, L. M., Davoli, M. A., Perlman, K., Aouabed, Z., Mash, D. C., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-38530-5 · Cited by 168
“5%and 15% (w/v) concentrations of iodixanol (batches 3F, 7F, 2F) and a stronger gradient using the 29% and 25% (w/v) concentrations of iodixanol(batches6F,8F,12F),aspreviouslypublished 78 ,andwefound the stronger gradient to perform better.”
Epigenetic Signaling in Psychiatric Disorders
Peña, C. J., Bagot, R. C., Labonté, B., & Nestler, E. J. (2014) · Journal of Molecular Biology · doi:10.1016/j.jmb.2014.03.016 · Cited by 163
Tissue of origin determines cancer-associated CpG island promoter hypermethylation patterns
Sproul, D., Kitchen, R. R., Nestor, C. E., Dixon, J. M., Sims, A. H., Harrison, D. J., Ramsahoye, B. H., & Meehan, R. R. (2012) · Genome Biology · doi:10.1186/gb-2012-13-10-r84 · Cited by 191
CpG island chromatin
Blackledge, N. P., & Klose, R. J. (2011) · Epigenetics · doi:10.4161/epi.6.2.13640 · Cited by 165
Ten-Eleven Translocation 1 (Tet1) Is Regulated by O-Linked N-Acetylglucosamine Transferase (Ogt) for Target Gene Repression in Mouse Embryonic Stem Cells
Shi, F.-T., Kim, H., Lu, W., He, Q., Liu, D., Goodell, M. A., Wan, M., & Songyang, Z. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.460386 · Cited by 168
Neuropathology of suicide: Recent findings and future directions
Lutz, P.-E., Mechawar, N., & Turecki, G. (2017) · Molecular Psychiatry · doi:10.1038/mp.2017.141 · Cited by 158
The early life social environment and DNA methylation: DNA methylation mediating the long-term impact of social environments early in life
Szyf, M. (2011) · Epigenetics · doi:10.4161/epi.6.8.16793 · Cited by 161
DNA methylation based biomarkers: Practical considerations and applications
Kit, A. H., Nielsen, H. M., & Tost, J. (2012) · Biochimie · doi:10.1016/j.biochi.2012.07.014 · Cited by 163
Imprinting and epigenetic changes in the early embryo
Weaver, J. R., Susiarjo, M., & Bartolomei, M. S. (2009) · Mammalian Genome · doi:10.1007/s00335-009-9225-2 · Cited by 161
Functions of DNA Methylation and Hydroxymethylation in Mammalian Development
Guibert, S., & Weber, M. (2013) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/b978-0-12-416027-9.00002-4 · Cited by 173
5-hydroxymethylcytosine accumulation in postmitotic neurons results in functional demethylation of expressed genes
Mellén, M., Ayata, P., & Heintz, N. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1708044114 · Cited by 151
“Discussion The discovery of 5hmC in the mammalian genome (2) has led to important insights into its role as an intermediate in passive and active cytosine demethylation in dividing cell populations (4, 38).”
BackgroundSelf-citation
Implications of Prenatal Steroid Perturbations for Neurodevelopment, Behavior, and Autism
Gore, A. C., Martien, K. M., Gagnidze, K., & Pfaff, D. W. (2014) · Endocrine Reviews · doi:10.1210/er.2013-1122 · Cited by 167
DNA demethylation, Tet proteins and 5-hydroxymethylcytosine in epigenetic reprogramming: An emerging complex story
Hill, P. W. S., Amouroux, R., & Hájková, P. (2014) · Genomics · doi:10.1016/j.ygeno.2014.08.012 · Cited by 161
Single-Cell 5-Formylcytosine Landscapes of Mammalian Early Embryos and ESCs at Single-Base Resolution
Zhu, C., Gao, Y., Guo, H., Xia, B., Song, J., Wu, X., Zeng, H., Kee, K., Tang, F., & Yi, C. (2017) · Cell stem cell · doi:10.1016/j.stem.2017.02.013 · Cited by 164
Environmental enrichment increases transcriptional and epigenetic differentiation between mouse dorsal and ventral dentate gyrus
Zhang, T., Keown, C. L., Wen, X., Li, J., Vousden, D. A., Anacker, C., Bhattacharyya, U., Ryan, R., Diorio, J. C., O’Toole, N., et al. (2018) · Nature Communications · doi:10.1038/s41467-017-02748-x · Cited by 162
DNA Hypomethylation and Hemimethylation in Cancer
Ehrlich, M., & Lacey, M. R. (2012) · Advances in experimental medicine and biology · doi:10.1007/978-1-4419-9967-2_2 · Cited by 163
Epigenetics in teleost fish: From molecular mechanisms to physiological phenotypes
Best, C., Ikert, H., Kostyniuk, D. J., Craig, P. M., Navarro‐Martín, L., Marandel, L., & Mennigen, J. A. (2018) · Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology · doi:10.1016/j.cbpb.2018.01.006 · Cited by 175
“is abundant in the brain of mice (Kriaucionis and Heintz, 2009) and zebrafish (Kamstra et al.”
Background
Epigenetics in Alzheimer’s Disease: Perspective of DNA Methylation
Qazi, T. J., Quan, Z., Mir, A., & Qing, H. (2018) · Molecular Neurobiology · doi:10.1007/s12035-016-0357-6 · Cited by 153
“In neurons, DNA hydroxymethylation can occur in result of oxidative stress or the action ten-eleven-translocation-1(TET1), which is a specific oxidative enzyme [21, 22].”
Background
Potential functional roles of DNA demethylation intermediates
Song, C.-X., & He, C. (2013) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2013.07.003 · Cited by 154
Differences in DNA methylation between human neuronal and glial cells are concentrated in enhancers and non-CpG sites
Kozlenkov, A., Roussos, P., Timashpolsky, A., Barbu, M., Rudchenko, S., Bibikova, M. V., Klotzle, B., Byne, W. M., Lyddon, R., Narzo, A. F. D., et al. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt838 · Cited by 159
Formation and determination of the oxidation products of 5-methylcytosine in RNA
Huang, W., Lan, M., Qi, C., Zheng, S.-J., Wei, S., Yuan, B., & Feng, Y. (2016) · Chemical Science · doi:10.1039/c6sc01589a · Cited by 154
Increased binding of MeCP2 to the GAD1 and RELN promoters may be mediated by an enrichment of 5-hmC in autism spectrum disorder (ASD) cerebellum
Zhubi, A., Chen, Y., Dong, E., Cook, E. H., Guidotti, A., & Grayson, D. R. (2014) · Translational Psychiatry · doi:10.1038/tp.2013.123 · Cited by 154
Developmental programming and epigenetics
Gabory, A., Attig, L., & Junien, C. (2011) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.110.000927 · Cited by 164
Genome-Scale Dna Methylation Analysis
Fouse, S. D., Nagarajan, R. P., & Costello, J. (2010) · Epigenomics · doi:10.2217/epi.09.35 · Cited by 154
The histone deacetylase SIRT6 controls embryonic stem cell fate via TET-mediated production of 5-hydroxymethylcytosine
Etchegaray, J., Chávez, L., Huang, Y., Ross, K. N., Choi, J., Martínez-Pastor, B., Walsh, R. M., Sommer, C., Lienhard, M., Gladden, A. D., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3147 · Cited by 158
Single-base resolution analysis of active DNA demethylation using methylase-assisted bisulfite sequencing
Wu, H., Wu, X., Shen, L., & Zhang, Y. (2014) · Nature Biotechnology · doi:10.1038/nbt.3073 · Cited by 157
A sensitive mass spectrometry method for simultaneous quantification of DNA methylation and hydroxymethylation levels in biological samples
Le, T. T., Kim, K.-P., Fan, G., & Faull, K. F. (2011) · Analytical Biochemistry · doi:10.1016/j.ab.2011.01.026 · Cited by 153
Hydroxyl-radical-induced oxidation of 5-methylcytosine in isolated and cellular DNA
Madugundu, G. S., Cadet, J., & Wagner, J. R. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku334 · Cited by 159
Changes in correlation between promoter methylation and gene expression in cancer
Moarii, M., Boeva, V., Vert, J., & Reyal, F. (2015) · BMC Genomics · doi:10.1186/s12864-015-1994-2 · Cited by 156
Nucleic acid modifications with epigenetic significance
Fu, Y., & He, C. (2012) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2012.10.002 · Cited by 149
Genome-wide loss of 5-hmC is a novel epigenetic feature of Huntington's disease
Wang, F., Yang, Y., Lin, X., Wang, J.-Q., Yong-sheng, W., Xie, W., Wang, D., Zhu, S., Liao, Y.-Q., Sun, Q., et al. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt214 · Cited by 155
Mitochondrial regulation of epigenetics and its role in human diseases
Minocherhomji, S., Tollefsbol, T. O., & Singh, K. K. (2012) · Epigenetics · doi:10.4161/epi.19547 · Cited by 151
Rett Syndrome: Crossing the Threshold to Clinical Translation
Katz, D. M., Bird, A., Coenraads, M., Gray, S. J., Menon, D. U., Philpot, B. D., & Tarquinio, D. C. (2016) · Trends in Neurosciences · doi:10.1016/j.tins.2015.12.008 · Cited by 150
Heterochromatin establishment in the context of genome-wide epigenetic reprogramming
Probst, A. V., & Almouzni, G. (2011) · Trends in Genetics · doi:10.1016/j.tig.2011.02.002 · Cited by 149
Epigenetic effects of stress and corticosteroids in the brain
Hunter, R. G. (2012) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2012.00018 · Cited by 150
Low values of 5‐hydroxymethylcytosine (5hmC), the “sixth base,” are associated with anaplasia in human brain tumors
Kraus, T. F. J., Globisch, D., Wagner, M., Eigenbrod, S., Widmann, D., Münzel, M., Müller, M., Pfaffeneder, T., Hackner, B., Feiden, W., et al. (2012) · International Journal of Cancer · doi:10.1002/ijc.27429 · Cited by 146
Sensitive and Simultaneous Determination of 5-Methylcytosine and Its Oxidation Products in Genomic DNA by Chemical Derivatization Coupled with Liquid Chromatography-Tandem Mass Spectrometry Analysis
Tang, Y., Zheng, S.-J., Qi, C., Feng, Y., & Yuan, B. (2015) · Analytical Chemistry · doi:10.1021/ac504786r · Cited by 144
Excision of 5-hydroxymethyluracil and 5-carboxylcytosine by the thymine DNA glycosylase domain: its structural basis and implications for active DNA demethylation
Hashimoto, H., Hong, S., Bhagwat, A. S., Zhang, X., & Cheng, X. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks845 · Cited by 147
Selective advantage of mutant stem cells in human clonal hematopoiesis is associated with attenuated response to inflammation and aging
Jakobsen, N. A., Turkalj, S., Zeng, A. G. X., Stoilova, B., Metzner, M., Rahmig, S., Nagree, M. S., Shah, S., Moore, R., Usukhbayar, B., et al. (2024) · Cell Stem Cell · doi:10.1016/j.stem.2024.05.010 · Cited by 130
DNA methylation, early life environment, and health outcomes
Mitchell, C., Schneper, L. M., & Notterman, D. A. (2016) · Pediatric Research · doi:10.1038/pr.2015.193 · Cited by 146
Differential Regulation of the Ten-Eleven Translocation (TET) Family of Dioxygenases by O-Linked β-N-Acetylglucosamine Transferase (OGT)
Zhang, Q., Liu, X., Gao, W., Li, P., Hou, J., Li, J., & Wong, J. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.524140 · Cited by 156
The genome-wide landscape of DNA methylation and hydroxymethylation in response to sleep deprivation impacts on synaptic plasticity genes
Massart, R., Freyburger, M., Suderman, M. J., Paquet, J., Helou, J. E., Bélanger-Nelson, E., Rachalski, A., Koumar, O. C., Carrier, J., Moshe Szyf, A., et al. (2014) · Translational Psychiatry · doi:10.1038/tp.2013.120 · Cited by 146
MeCP2 recognizes cytosine methylated tri-nucleotide and di-nucleotide sequences to tune transcription in the mammalian brain
Lagger, S., Connelly, J. C., Schweikert, G., Webb, S., Selfridge, J., Ramsahoye, B. H., Yu, M., DeSousa, D., Seiser, C., He, C., et al. (2017) · PLoS Genetics · doi:10.1371/journal.pgen.1006793 · Cited by 146
“The predominant methylated sequence is the di-nucleotide CG, but in adult brain mCA [3] and hmCG [17,28] are implicated as binding partners of MeCP2.”
Background
The preconception environment and sperm epigenetics
Marcho, C., Oluwayiose, O. A., & Pilsner, J. R. (2020) · Andrology · doi:10.1111/andr.12753 · Cited by 153
TET3 Is Recruited by REST for Context-Specific Hydroxymethylation and Induction of Gene Expression
Perera, A., Eisen, D., Wagner, M., Laube, S. K., Künzel, A. F., Koch, S., Steinbacher, J., Schulze, E., Splith, V., Mittermeier, N., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.03.020 · Cited by 145
The APOE Gene is Differentially Methylated in Alzheimer’s Disease
Foraker, J. E., Millard, S. P., Leong, L., Thomson, Z., Chen, S., Keene, C. D., Bekris, L. M., & Yu, C. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-143060 · Cited by 143
Increased 5-Methylcytosine and Decreased 5-Hydroxymethylcytosine Levels are Associated with Reduced Striatal A2AR Levels in Huntington’s Disease
Villar-Menéndez, I., Blanch, M., Tyebji, S., Pereira‐Veiga, T., Albasanz, J. L., Martı́n, M., Ferrer, I., Pérez‐Navarro, E., & Barrachina, M. (2013) · NeuroMolecular Medicine · doi:10.1007/s12017-013-8219-0 · Cited by 144
Mechanism and Stem‐Cell Activity of 5‐Carboxycytosine Decarboxylation Determined by Isotope Tracing
Schießer, S., Hackner, B., Pfaffeneder, T., Müller, M., Hagemeier, C., Truß, M., & Carell, T. (2012) · Angewandte Chemie International Edition · doi:10.1002/anie.201202583 · Cited by 143
DNA methylation map of mouse and human brain identifies target genes in Alzheimer’s disease
Sanchez-Mut, J. V., Aso, E., Panayotis, N., Lott, I., Dierssen, M., Rabano, A., Urdinguio, R. G., Fernandez, A. F., Astudillo, A., Martin-Subero, J. I., et al. (2013) · Brain · doi:10.1093/brain/awt237 · Cited by 144
Epigenetic regulation mechanisms of microRNA expression
Morales, S., Monzó, M., & Navarro, A. (2017) · BioMolecular Concepts · doi:10.1515/bmc-2017-0024 · Cited by 159
“DNA hydroxymethylation is a recently discovered modification of CpG dinucleotides that involves the addition of a hydroxyl group on 5-methylcytosines (5mCs) to produce 5-hydroxymethylcytosine (5hmCs) (65, 66).”
Background
Targeting DNA Methylation with Small Molecules: What’s Next?
Erdmann, A., Halby, L., Fahy, J., & Arimondo, P. B. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm500843d · Cited by 149
DNA Methylation in Systemic Lupus Erythematosus
Hedrich, C. M., Mäbert, K., Rauen, T., & Tsokos, G. C. (2016) · Epigenomics · doi:10.2217/epi-2016-0096 · Cited by 142
Epigenetic regulation of smooth muscle cell plasticity
Liu, R., Leslie, K. L., & Martin, K. A. (2014) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2014.06.004 · Cited by 142
Krebs cycle intermediates regulate DNA and histone methylation: Epigenetic impact on the aging process
Salminen, A., Kauppinen, A., Hiltunen, M. O., & Kaarniranta, K. (2014) · Ageing Research Reviews · doi:10.1016/j.arr.2014.05.004 · Cited by 145
Childhood adversity and DNA methylation of genes involved in the hypothalamus-pituitary-adrenal axis and immune system: whole-genome and candidate-gene associations
Bick, J., Naumova, O., Hunter, S., Barbot, B., Lee, M., Luthar, S. S., Raefski, A., & Grigorenko, E. L. (2012) · Development and Psychopathology · doi:10.1017/s0954579412000806 · Cited by 140
Age‐Dependent Levels of 5‐Methyl‐, 5‐Hydroxymethyl‐, and 5‐Formylcytosine in Human and Mouse Brain Tissues
Wagner, M., Steinbacher, J., Kraus, T. F. J., Michalakis, S., Hackner, B., Pfaffeneder, T., Perera, A., Müller, M., Giese, A., Kretzschmar, H. A., et al. (2015) · Angewandte Chemie International Edition · doi:10.1002/anie.201502722 · Cited by 136
Regulation of chromatin structure in memory formation
Roth, T. L., & Sweatt, J. D. (2009) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2009.05.011 · Cited by 138
Quantitative assessment of Tet-induced oxidation products of 5-methylcytosine in cellular and tissue DNA
Liu, S., Wang, J., Su, Y., Guerrero, C. R., Zeng, Y., Mitra, D., Brooks, P. J., Fisher, D. E., Song, H., & Wang, Y. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt360 · Cited by 140
Tet3 Reads 5-Carboxylcytosine through Its CXXC Domain and Is a Potential Guardian against Neurodegeneration
Jin, S.-G., Zhang, Z.-M., Dunwell, T. L., Harter, M. R., Wu, X., Johnson, J., Li, Z., Liu, J., Szabó, P. E., Lu, Q., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2015.12.044 · Cited by 138
TET Enzymes and 5hmC in Adaptive and Innate Immune Systems
Lio, C. J., & Rao, A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00210 · Cited by 144
“5hmC, the so-called 6th base, is a stable epigenetic modification that accounts for 1–10% of 5mC depending on the cell type:∼10% in embryonic stem cells (6) and as high as 40% in Purkinje neurons (7).”
Background
Cytosine-5-methyltransferases add aldehydes to DNA
Liutkevičiūtė, Z., Lukinavičius, G., Masevičius, V., Daujotyte, D., & Klimašauskas, S. (2009) · Nature Chemical Biology · doi:10.1038/nchembio.172 · Cited by 137
Silencing of endogenous retroviruses: when and why do histone marks predominate?
Leung, D., & Lorincz, M. C. (2011) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2011.11.006 · Cited by 140
Epigenetic Regulations in Neuropsychiatric Disorders
Kuehner, J. N., Bruggeman, E. C., Wen, Z., & Yao, B. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.00268 · Cited by 144
Quantification of 5-Methylcytosine and 5-Hydroxymethylcytosine in Genomic DNA from Hepatocellular Carcinoma Tissues by Capillary Hydrophilic-Interaction Liquid Chromatography/Quadrupole TOF Mass Spectrometry
Chen, M.-L., Shen, F., Huang, W., Qi, J., Wang, Y., Feng, Y., Liu, S.-M., & Yuan, B. (2013) · Clinical Chemistry · doi:10.1373/clinchem.2012.193938 · Cited by 135
Alzheimer’s disease-associated (hydroxy)methylomic changes in the brain and blood
Lardenoije, R., Roubroeks, J. A. Y., Pishva, E., Leber, M., Wagner, H., Iatrou, A., Smith, A. R., Smith, R. G., Eijssen, L., Kleineidam, L., et al. (2019) · Clinical Epigenetics · doi:10.1186/s13148-019-0755-5 · Cited by 135
Tissue-specific 5-hydroxymethylcytosine landscape of the human genome
He, B., Zhang, C., Zhang, X., Fan, Y., Zeng, H., Liu, J., Meng, H., Bai, D., Peng, J., Zhang, Q., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24425-w · Cited by 135
Enhanced 5-methylcytosine detection in single-molecule, real-time sequencing via Tet1 oxidation
Clark, T. A., Lu, X., Luong, K., Dai, Q., Boitano, M., Turner, S. W., He, C., & Korlach, J. (2013) · BMC Biology · doi:10.1186/1741-7007-11-4 · Cited by 139
Phosphorylation of TET Proteins Is Regulated via O-GlcNAcylation by the O-Linked N-Acetylglucosamine Transferase (OGT)
Bauer, C., Göbel, K., Nagaraj, N., Colantuoni, C., Wang, M., Müller, U., Kremmer, E., Rottach, A., & Leonhardt, H. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.605881 · Cited by 144
Epigenetic mechanisms in Alzheimer's disease: Implications for pathogenesis and therapy
Wang, J., Yu, J., Tan, M., Jiang, T., & Tan, L. (2013) · Ageing Research Reviews · doi:10.1016/j.arr.2013.05.003 · Cited by 140
5-Hydroxymethylcytosine: generation, fate, and genomic distribution
Shen, L., & Zhang, Y. (2013) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2013.02.017 · Cited by 134
Quantitative LC–MS Provides No Evidence for m6dA or m4dC in the Genome of Mouse Embryonic Stem Cells and Tissues
Schiffers, S., Ebert, C., Rahimoff, R., Kosmatchev, O., Steinbacher, J., Bohne, A., Spada, F., Michalakis, S., Nickelsen, J., Müller, M., et al. (2017) · Angewandte Chemie International Edition · doi:10.1002/anie.201700424 · Cited by 136
Nanoparticles in food. Epigenetic changes induced by nanomaterials and possible impact on health
Smolková, B., Yamani, N. E., Collins, A. R., Gutleb, A. C., & Dušinská, M. (2014) · Food and Chemical Toxicology · doi:10.1016/j.fct.2014.12.015 · Cited by 138
Loss of 5-hydroxymethylcytosine in cancer: Cause or consequence?
Ficz, G., & Gribben, J. G. (2014) · Genomics · doi:10.1016/j.ygeno.2014.08.017 · Cited by 135
DNA Methylation: A Timeline of Methods and Applications
Harrison, A. J., & Parle‐McDermott, A. (2011) · Frontiers in Genetics · doi:10.3389/fgene.2011.00074 · Cited by 135
Methamphetamine Downregulates Striatal Glutamate Receptors via Diverse Epigenetic Mechanisms
Jayanthi, S., McCoy, M. T., Chen, B., Britt, J. P., Kourrich, S., Yau, H., Ladenheim, B., Krasnova, I. N., Bonci, A., & Cadet, J. L. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.09.034 · Cited by 136
Epigenetics and Cardiovascular Disease
Webster, A., Yan, M. S.-C., & Marsden, P. A. (2012) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2012.10.023 · Cited by 136
The Role of Epigenetic Mechanisms in the Regulation of Gene Expression in the Nervous System
Cholewa-Waclaw, J., Bird, A. P., von Schimmelmann, M. J., Schaefer, A., Yu, H., Song, H., Madabhushi, R., & Tsai, L. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.2492-16.2016 · Cited by 137
“Accompanying the rediscovery of another DNA modification, 5-hydroxylmethylation (5hmC), in adult mouse neurons (Kriaucionis and Heintz, 2009), Tet proteins were identified to oxidize 5mC to 5hmC (Tahiliani et al., 2009; Ito et al., 2010).”
Background
A multi-tissue analysis identifies HLA complex group 9 gene methylation differences in bipolar disorder
Kaminsky, Z. A., Tochigi, M., Jia, P., Pal, M., Mill, J. S., Kwan, A., Ioshikhes, I. P., Vincent, J. B., Kennedy, J. L., Strauss, J., et al. (2011) · Molecular Psychiatry · doi:10.1038/mp.2011.64 · Cited by 135
Genomic insights into cancer-associated aberrant CpG island hypermethylation
Sproul, D., & Meehan, R. R. (2013) · Briefings in Functional Genomics · doi:10.1093/bfgp/els063 · Cited by 135
DNA Methylation, Behavior and Early Life Adversity
Szyf, M. (2013) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2013.06.004 · Cited by 147
Cell cycle and p53 gate the direct conversion of human fibroblasts to dopaminergic neurons
Jiang, H., Xu, Z., Zhong, P., Ren, Y., Liang, G., Schilling, H. A., Hu, Z., Zhang, Y., Wang, X., Chen, S., et al. (2015) · Nature Communications · doi:10.1038/ncomms10100 · Cited by 133
Detection of Human Urinary 5-Hydroxymethylcytosine by Stable Isotope Dilution HPLC-MS/MS Analysis
Yin, R., Mo, J., Lü, M., & Wang, H. (2014) · Analytical Chemistry · doi:10.1021/ac5038895 · Cited by 133
The Epigenetics of Epilepsy and Its Progression
Hauser, R. M., Henshall, D. C., & Lubin, F. D. (2017) · The Neuroscientist · doi:10.1177/1073858417705840 · Cited by 135
“The role of 5-hmc in the brain is of exceptional interest from a neuroscience perspective because this mark is abundantly present in the brain, indicating a likely prevalent role as a major epigenetic regulator of neuronal activity (Kriaucionis and Heintz 2009; Munzel and others 2010).”
Background
A unique role for DNA (hydroxy)methylation in epigenetic regulation of human inhibitory neurons
Kozlenkov, A., Li, J., Apontes, P., Hurd, Y. L., Byne, W. M., Koonin, E. V., Wegner, M., Mukamel, E. A., & Dracheva, S. (2018) · Science Advances · doi:10.1126/sciadv.aau6190 · Cited by 103
“In postmitotic neuronal genomes, non-CG methylcytosine (mCH) and hmC accumulate to a significantly higher level than in other differentiated tissues (7, 8), which is a distinct feature of the brain’s epigenome (9–12).”
Background
Mass Spectrometry of Structurally Modified DNA
Tretyakova, N. Y., Villalta, P. W., & Kotapati, S. (2013) · Chemical Reviews · doi:10.1021/cr300391r · Cited by 133
Epigenetic control of gene regulation during development and disease: A view from the retina
Corso‐Díaz, X., Jaeger, C., Chaitankar, V., & Swaroop, A. (2018) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2018.03.002 · Cited by 130
“Other forms of methylation (such as 5hmC) are abundant in neurons (Kriaucionis and Heintz, 2009) and accumulate during neuronal maturation in the brain (Lister et al.”
Background
Genome-wide CpG density and DNA methylation analysis method (MeDIP, RRBS, and WGBS) comparisons.
Beck, D., Maamar, M. B., & Skinner, M. K. (2022) · PubMed Central · doi:10.1080/15592294.2021.1924970 · Cited by 57
“A misconception with 5hmc is that it is common in cell types,; however,it is primarily present in appreciable levels in stem cells such as the early embryo or primordial germ cells where DNA methylation erasure is predominant, and certain post mitotic differentiated neurons [38].”
Background
Effect of aging on 5-hydroxymethylcytosine in the mouse hippocampus
Chen, H., Dzitoyeva, S., & Manev, H. (2012) · Restorative Neurology and Neuroscience · doi:10.3233/rnn-2012-110223 · Cited by 131
Cognitive neuroepigenetics: A role for epigenetic mechanisms in learning and memory
Day, J. J., & Sweatt, J. D. (2010) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2010.12.008 · Cited by 137
Epigenetic regulation in pluripotent stem cells: a key to breaking the epigenetic barrier
Watanabe, A., Yamada, Y., & Yamanaka, S. (2012) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2012.0292 · Cited by 133
DNA Modification under Mild Conditions by Suzuki–Miyaura Cross‐Coupling for the Generation of Functional Probes
Lercher, L., McGouran, J. F., Kessler, B. M., Schofield, C. J., & Davis, B. G. (2013) · Angewandte Chemie International Edition · doi:10.1002/anie.201304038 · Cited by 130
The chemistries and consequences of DNA and RNA methylation and demethylation
Traube, F. R., & Carell, T. (2017) · RNA Biology · doi:10.1080/15476286.2017.1318241 · Cited by 131
“032% of all nucleotides in embryonic stem (ES) cells.(45,47) The highest 5hmdC levels in fully differentiated tissues were found in the brain with up to 1% of all cytosines.”
Background
Tet Enzymes, Variants, and Differential Effects on Function
Melamed, P., Yosefzon, Y., David, C., Tsukerman, A., & Pnueli, L. (2018) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2018.00022 · Cited by 130
“…of 5mC and 1% of all cytosine in human brain), mostly in transcribed sequences, and in regions near promoters and enhancers, where it correlates positively with gene expression (Kriaucionis and Heintz, 2009; Münzel et al., 2011; Szulwach et al., 2011b; Colquitt et al., 2013; Hahn et al., 2013).”
Background
Epigenetic and Neurological Impairments Associated with Early Life Exposure to Persistent Organic Pollutants
Grova, N., Schroeder, H., Olivier, J. L., & Turner, J. D. (2019) · International Journal of Genomics · doi:10.1155/2019/2085496 · Cited by 138
“In cerebellar Purkinje cells, 5hmC levels are ~40% of 5mC levels compared to ~10% elsewhere in the body [164].”
Background
An atomic model of Zfp57 recognition of CpG methylation within a specific DNA sequencePreprint
Liu, Y., Toh, H., Sasaki, H., Zhang, X., & Cheng, X. (2012) · Genes & Development · doi:10.1101/gad.202200.112 · Cited by 128
5-Hydroxymethylcytosine: A stable or transient DNA modification?
Hahn, M. A., Szabó, P. E., & Pfeifer, G. P. (2014) · Genomics · doi:10.1016/j.ygeno.2014.08.015 · Cited by 133

Authors: Kriaucionis, S., & Heintz, N.
Affiliations: Laboratory of Molecular Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
Howard Hughes Medical Institute (US)
Corresponding author: Heintz, Nathaniel
ORCID: Heintz, Nathaniel
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2009-05-15
Volume: 324
Issue: 5929
Pages: 929-930
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1169786
PMC: PMC3263819
OpenAlex: W2152451432
Cited by: 2,700
References: 14
Citations by year: 2026: 53 · 2025: 69 · 2024: 84 · 2023: 93 · 2022: 112 · 2021: 137 · 2020: 107 · 2019: 150 · 2018: 190 · 2017: 218 · 2016: 236 · 2015: 220 · 2014: 259 · 2013: 252 · 2012: 202
FWCI: 69.99
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Howard Hughes Medical Institute
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
Keywords: 5-hydroxymethylcytosine, Purkinje cells, cerebellar granule cells, DNA methylation, epigenetic regulation, brain DNA, nucleotide composition
MeSH terms: Animals, Brain Chemistry, Cell Line, Cerebellum, Chromatography, High Pressure Liquid, Chromatography, Thin Layer, Cytosine, Deoxycytidine, DNA, DNA Damage, Humans, Purkinje Cells, Mass Spectrometry, 5-Methylcytosine, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

The Nuclear DNA Base 5-Hydroxymethylcytosine Is Present in Purkinje Neurons and the Brain

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks