Active chromatin and transcription play a key role in chromosome partitioning into topologically associating domains
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 conserv...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Cold Spring Harbor Laboratory Press
2017
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| Online Access: | http://hdl.handle.net/1721.1/110522 https://orcid.org/0000-0002-5320-2728 |
| _version_ | 1826205353941925888 |
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| author | Ulianov, Sergey V. Khrameeva, Ekaterina E. Gavrilov, Alexey A. Flyamer, Ilya M. Kos, Pavel Mikhaleva, Elena A. Penin, Aleksey A. Logacheva, Maria D. Chertovich, Alexander Gelfand, Mikhail S. Shevelyov, Yuri Y. Razin, Sergey V. Imakaev, Maksim Viktorovich |
| author2 | Massachusetts Institute of Technology. Department of Physics |
| author_facet | Massachusetts Institute of Technology. Department of Physics Ulianov, Sergey V. Khrameeva, Ekaterina E. Gavrilov, Alexey A. Flyamer, Ilya M. Kos, Pavel Mikhaleva, Elena A. Penin, Aleksey A. Logacheva, Maria D. Chertovich, Alexander Gelfand, Mikhail S. Shevelyov, Yuri Y. Razin, Sergey V. Imakaev, Maksim Viktorovich |
| author_sort | Ulianov, Sergey V. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T13:11:20Z |
| format | Article |
| id | mit-1721.1/110522 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:11:20Z |
| publishDate | 2017 |
| publisher | Cold Spring Harbor Laboratory Press |
| record_format | dspace |
| spelling | mit-1721.1/1105222022-09-28T12:30:50Z Active chromatin and transcription play a key role in chromosome partitioning into topologically associating domains Ulianov, Sergey V. Khrameeva, Ekaterina E. Gavrilov, Alexey A. Flyamer, Ilya M. Kos, Pavel Mikhaleva, Elena A. Penin, Aleksey A. Logacheva, Maria D. Chertovich, Alexander Gelfand, Mikhail S. Shevelyov, Yuri Y. Razin, Sergey V. Imakaev, Maksim Viktorovich Massachusetts Institute of Technology. Department of Physics Imakaev, Maksim Viktorovich 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. 2017-07-07T14:24:59Z 2017-07-07T14:24:59Z 2015-10 2015-06 Article http://purl.org/eprint/type/JournalArticle 1088-9051 1549-5469 http://hdl.handle.net/1721.1/110522 Ulianov, Sergey V.; Khrameeva, Ekaterina E.; Gavrilov, Alexey A.; Flyamer, Ilya M.; Kos, Pavel; Mikhaleva, Elena A.; Penin, Aleksey A. et al. "Active chromatin and transcription play a key role in chromosome partitioning into topologically associating domains." Genome Research 26 (October 2015): 70-84 © 2016 Ulianov et al https://orcid.org/0000-0002-5320-2728 en_US http://dx.doi.org/10.1101/gr.196006.115 Genome Research Creative Commons Attribution-NonCommercial 4.0 International http://creativecommons.org/licenses/by-nc/4.0/ application/pdf Cold Spring Harbor Laboratory Press Cold Spring Harbor Laboratory Press |
| spellingShingle | Ulianov, Sergey V. Khrameeva, Ekaterina E. Gavrilov, Alexey A. Flyamer, Ilya M. Kos, Pavel Mikhaleva, Elena A. Penin, Aleksey A. Logacheva, Maria D. Chertovich, Alexander Gelfand, Mikhail S. Shevelyov, Yuri Y. Razin, Sergey V. Imakaev, Maksim Viktorovich Active chromatin and transcription play a key role in chromosome partitioning into topologically associating domains |
| title | Active chromatin and transcription play a key role in chromosome partitioning into topologically associating domains |
| title_full | Active chromatin and transcription play a key role in chromosome partitioning into topologically associating domains |
| title_fullStr | Active chromatin and transcription play a key role in chromosome partitioning into topologically associating domains |
| title_full_unstemmed | Active chromatin and transcription play a key role in chromosome partitioning into topologically associating domains |
| title_short | Active chromatin and transcription play a key role in chromosome partitioning into topologically associating domains |
| title_sort | active chromatin and transcription play a key role in chromosome partitioning into topologically associating domains |
| url | http://hdl.handle.net/1721.1/110522 https://orcid.org/0000-0002-5320-2728 |
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