The 3D Genome as Moderator of Chromosomal Communication
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Proper expression of genes requires communication with their regulatory elements that can be located elsewhere along the chromosome. The physics of chromatin fibers imposes a range of constraints on such communication. The molecular and biophysical mechanisms by which chromosomal communication is established, or prevented, have become a topic of intense study, and important roles for the spatial organization of chromosomes are being discovered. Here we present a view of the interphase 3D genome characterized by extensive physical compartmentalization and insulation on the one hand and facilitated long-range interactions on the other. We propose the existence of topological machines dedicated to set up and to exploit a 3D genome organization to both promote and censor communication along and between chromosomes.
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The observed contact probability trend is consistent with previous estimations and is representative of the contact probabilities experienced by promoters in mES cells.
“This is consistent with previous estimations33 confirmed using cross-linking and ligation-free methods34 and is representative of the contact probabilities experienced by promoters in mES cells (Extended Data Fig. 2b, c).”
From Nonlinear control of transcription through enhancer–promoter interactions (2022) · cites this paper as [33]
By regulating contact probability, TADs appear to be one of the determinants of functional and specific enhancer-promoter interactions.
“Instead, by regulating contact probability, TADs appear to be one of the determinants of functional and specific enhancer-promoter interactions.29”
From Recent evidence that TADs and chromatin loops are dynamic structures (2018) · cites this paper as [29]
Two loci only contact each other ∼2-fold more frequently if they are within the same TAD instead of in different TADs.
“Even though two loci only contact each other ∼2-fold more frequently if they are within the same TAD instead of in different TADs,29”
From Recent evidence that TADs and chromatin loops are dynamic structures (2018) · cites this paper as [29]
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- Goloborodko A Marko JF Mirny LA Mitotic chromosome compaction via active loop etrusion 2015 bioRxiv doi: http://dx.doi.org/10.1101/021642 PMC4880799 27224481 · DOI
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“Beyond the information stored in the sequence of the genome, the 3D organization of eukaryotic (Kempfer and Pombo, 2019) and bacterial (Dame et al., 2019; Lioy et al., 2021) genomes plays a role in cellular behavior (Dekker and Mirny, 2016).”
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Choppavarapu, L., Nosirov, B., Kahn, M., & Jin, V. X. (2026) · Cancers · doi:10.3390/cancers18213416
- Authors
- Dekker, J., & Mirny, L.
- Affiliations
- Howard Hughes Medical Institute (US)
- Massachusetts Institute of Technology (US)
- Corresponding author
- Dekker, Job
- Mirny, Leonid
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2016-03
- Volume
- 164
- Issue
- 6
- Pages
- 1110-1121
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4788811
- OpenAlex
- W2295297857
- Cited by
- 937
- References
- 123
- Citations by year
- 2026: 63 · 2025: 73 · 2024: 69 · 2023: 73 · 2022: 86 · 2021: 105 · 2020: 112 · 2019: 102 · 2018: 112 · 2017: 95 · 2016: 45 · 2015: 1
- FWCI
- 10.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- PMC
- Funders
- Howard Hughes Medical Institute
- National Institute on Drug Abuse (U01DA040588)
- National Human Genome Research Institute (U54HG007010, U01HG007910, R01HG003143)
- National Cancer Institute (U54CA193419)
- National Institute of General Medical Sciences (R01GM114190, R01GM112720)
- National Institute of Allergy and Infectious Diseases (R01AI117839, U01 R01 AI 117839)
- National Institute of Diabetes and Digestive and Kidney Diseases (U54DK107980)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Keywords
- 3D genome organization, long-range interactions, chromatin compartmentalization, chromatin insulation, interphase, gene expression regulation, chromosomal architecture
- MeSH terms
- CCCTC-Binding Factor, Adenosine Triphosphatases, Animals, Chromosomes, DNA-Binding Proteins, Female, Humans, Mitosis, Repressor Proteins, Genome, Multiprotein Complexes, X Chromosome Inactivation
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