Active chromatin and transcription play a key role in chromosome partitioning into topologically associating domains

Ulianov, S.; Khrameeva, E.; Gavrilov, A.; Flyamer, I.; Kos, P.; Mikhaleva, E.; Penin, A.; Logacheva, M.; Imakaev, M.; Chertovich, A.; Gelfand, M.; Shevelyov, Y.; Razin, S.

Авторы: Ulianov SV, Khrameeva EE, Gavrilov AA, Flyamer IM, Kos P., Mikhaleva EA, Penin AA, Logacheva MD, Imakaev MV, Chertovich A., Gelfand MS, Shevelyov YY, Razin SV
Журнал: Genome Research
Том: 26
Год издания: 2016
Издательство: Cold Spring Harbor Laboratory Press
Местоположение издательства: United States
Первая страница: 70
Последняя страница: 84
DOI: 10.1101/gr.196006.115
Аннотация: 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 PolyA+ 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 interbands 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.
Добавил в систему: Разин Сергей Владимирович

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Active chromatin and transcription play a key role in chromosome partitioning into topologically associating domainsстатья

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