Active chromatin and transcription play a key role in chromosome partitioning into topologically associating domains
Open accessAbstract
Recent advances enabled by the Hi-C technique have unraveled many principles of chromosomal folding that were subsequently linked to disease and gene regulation. In particular, Hi-C revealed that chromosomes of animals are organized into topologically associating domains (TADs), evolutionary conserved compact chromatin domains that influence gene expression. Mechanisms that underlie partitioning of the genome into TADs remain poorly understood. To explore principles of TAD folding in Drosophila melanogaster , we performed Hi-C and poly(A) + RNA-seq in four cell lines of various origins (S2, Kc167, DmBG3-c2, and OSC). Contrary to previous studies, we find that regions between TADs (i.e., the inter-TADs and TAD boundaries) in Drosophila are only weakly enriched with the insulator protein dCTCF, while another insulator protein Su(Hw) is preferentially present within TADs. However, Drosophila inter-TADs harbor active chromatin and constitutively transcribed (housekeeping) genes. Accordingly, we find that binding of insulator proteins dCTCF and Su(Hw) predicts TAD boundaries much worse than active chromatin marks do. Interestingly, inter-TADs correspond to decompacted inter-bands of polytene chromosomes, whereas TADs mostly correspond to densely packed bands. Collectively, our results suggest that TADs are condensed chromatin domains depleted in active chromatin marks, separated by regions of active chromatin. We propose the mechanism of TAD self-assembly based on the ability of nucleosomes from inactive chromatin to aggregate, and lack of this ability in acetylated nucleosomal arrays. Finally, we test this hypothesis by polymer simulations and find that TAD partitioning may be explained by different modes of inter-nucleosomal interactions for active and inactive chromatin.
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It has been proposed that Drosophila TADs are formed by condensation of nucleosomes and thus should be rather called 'compartmental domains'.
“It has been proposed that Drosophila TADs are formed by condensation of nucleosomes [123] and thus should be rather called “compartmental domains” [124].”
From Enhancer Function in the 3D Genome (2023) · cites this paper as [123]
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“One possibility is the establishment of long-range contacts between enhancers and their cognate promoters, as well as loops between pairs of insulators (Doyle et al. 2014).”
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Self-citation
- Authors
- Ulianov, S. V., Khrameeva, E. E., Gavrilov, A. A., Flyamer, I. M., Kos, P., Mikhaleva, E. A., Penin, A. A., Logacheva, M. D., Imakaev, M. V., Chertovich, A., Gelfand, M. S., Shevelyov, Y. Y., & Razin, S. V.
- Affiliations
- Lomonosov Moscow State University (RU)
- Skolkovo Institute of Science and Technology (RU)
- Russian Academy of Sciences (RU)
- Institute of Molecular Genetics (RU)
- Massachusetts Institute of Technology (US)
- Corresponding author
- Razin, Sergey V.
- ORCID
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2015-10-30
- Volume
- 26
- Issue
- 1
- Pages
- 70-84
- ISSN
- 1088-9051 (ISSN-L)
- 1549-5469
- PMC
- PMC4691752
- OpenAlex
- W2172400873
- Cited by
- 388
- References
- 12
- Citations by year
- 2026: 12 · 2025: 20 · 2024: 31 · 2023: 25 · 2022: 34 · 2021: 50 · 2020: 50 · 2019: 38 · 2018: 55 · 2017: 42 · 2016: 28 · 2015: 3
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genome Research (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Russian Foundation for Basic Research (13-00-40086-K, 14-04-91331, 14-04-00010, 14-03-00825)
- Presidium of the Russian Academy of Sciences
- Russian Science Foundation (14-14-01088, 14-24-00155)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- topologically associating domains, chromosome segregation, chromatin folding, insulator proteins, Su(Hw), active chromatin, TAD boundaries, polytene chromosomes, nucleosome compaction, chromatin acetylation, Drosophila melanogaster, gene expression regulation
- MeSH terms
- Animals, Cell Line, Chromatin, Chromosome Mapping, Computer Simulation, Drosophila melanogaster, Models, Molecular, Nucleosomes, Transcription, Genetic, Sequence Analysis, RNA, Chromatin Assembly and Disassembly, Genome, Insect, Polytene Chromosomes
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