Complex multi-enhancer contacts captured by genome architecture mapping

Beagrie, Robert A.; Scialdone, Antonio; Schueler, Markus; Kraemer, Dorothee; Chotalia, Mita; Xie, Shaoping; Barbieri, Mariano; Santiago, Inês de; Lavitas, Liron‐Mark; Branco, Miguel R.; Fraser, James A.; Dostie, Josée; Gamé, Laurence; Dillon, Niall; Edwards, Paul A.W.; Nicodemi, Mario; Pombo, Ana

doi:10.1038/nature21411

Cited by 614 publications

(693 citation statements)

References 64 publications

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“…This implies that compartmentalization is capable of inducing intrachromosomal loops and interchromosomal links at rapid rates, comparable to those of loop-domain formation. (Our findings may be related to those of other studies, which have noted enhanced interactions between higher-order intrachromosomal interactions between domains containing superenhancers (Beagrie et al, 2017). )…”

Section: Discussionsupporting

confidence: 90%

Cohesin Loss Eliminates All Loop Domains

Rao

Huang

Hilaire

et al. 2017

Cell

1,589

223

1,924

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SUMMARY The human genome folds to create thousands of intervals, called “contact domains,” that exhibit enhanced contact frequency within themselves. “Loop domains” form because of tethering between two loci – almost always bound by CTCF and cohesin – lying on the same chromosome. “Compartment domains” form when genomic intervals with similar histone marks co-segregate. Here, we explore the effects of degrading cohesin. All loop domains are eliminated, but neither compartment domains nor histone marks are affected. Loss of loop domains does not lead to widespread ectopic gene activation, but does affect a significant minority of active genes. In particular, cohesin loss causes superenhancers to co-localize, forming hundreds of links within and across chromosomes, and affecting the regulation of nearby genes. We then restore cohesin and monitor the re-formation of each loop. Although reformation rates vary greatly, many megabase-sized loops recovered in under an hour, consistent with a model where loop extrusion is rapid.

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Section: Discussionsupporting

confidence: 90%

Cohesin Loss Eliminates All Loop Domains

Rao

Huang

Hilaire

et al. 2017

Cell

1,589

223

1,924

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“…Such a colocalization of transcribed DNA is supported by recent studies of DNA-DNA contacts. For example, DNA-DNA contacts are significantly enriched in highly transcribed DNA elements (Rao et al, 2014;Beagrie et al, 2017), transcription levels predict DNA-DNA contact frequencies (Rowley et al, 2017), and long-range DNA-DNA contacts depend on ongoing transcription (Hug et al, 2017). At the megabase scale, the genome can be assigned to regions that are defined by an elevated internal contact frequency (Lieberman-Aiden et al, 2009).…”

Section: Microenvironments Might Explain Major Features Of Genome Arcmentioning

confidence: 99%

“…In addition to affecting the degree of chromatin compaction, transcription has long been suggested to result in DNA-DNA contacts (Cook, 1999). Indeed, genome-wide analyses of DNA-DNA contacts have revealed that transcribed elements are enriched amongst these contacts (Beagrie et al, 2017;Rowley et al, 2017). Moreover, long-range contacts between transcribed regions are lost when transcription is inhibited (Schoenfelder et al, 2010;Hug et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Transcription organizes euchromatin similar to an active microemulsion

Hilbert

Sato

Kimurâ

et al. 2017

Preprint

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Graphical abstract HighlightsThe copyright holder for this preprint (which was . http://dx.doi.org/10.1101/234112 doi: bioRxiv preprint first posted online Dec. 15, 2017; Page 2 of 46 SummaryThe three-dimensional organization of the genome is essential for development and health. Although the organization of euchromatin (transcriptionally permissive chromatin) dynamically adjusts to changes in transcription, the underlying mechanisms remain elusive. Here, we studied how transcription organizes euchromatin, using experiments in zebrafish embryonic cells and theory. We show that transcription establishes an interspersed pattern of chromatin domains and RNA-enriched microenvironments. Specifically, accumulation of RNA in the vicinity of transcription sites creates microenvironments that locally remodel chromatin by displacing not transcribed chromatin. Ongoing transcriptional activity stabilizes the interspersed pattern of chromatin domains and RNA-enriched microenvironments by establishing contacts between chromatin and RNA. We explain our observations with an active microemulsion model based on two macromolecular mechanisms: RNA/RNA-binding protein complexes generally segregate from chromatin, while transcribed chromatin is retained among RNA/RNA-binding protein accumulations. We propose that microenvironments might be central to genome architecture and serve as gene regulatory hubs.

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“…For instance, transcriptionally active regions are often co-localised in super-enhancer hubs [8] or transcription factories [14], whereas transcriptionally inactive regions may form large heterochromatic foci [15], mega-base (Mbp) size lamin-associated domains [16] or Barr [17] and Polycomb bodies [18].…”

Section: Introductionmentioning

confidence: 99%

“…The epigenetic patterning of chromatin -the fibre made of DNA wrapped around histone proteins [1] -has been shown to strongly correlate with the three-dimensional (3D) nuclear organisation of interphase chromosomes [7][8][9][10][11][12][13]. For instance, transcriptionally active regions are often co-localised in super-enhancer hubs [8] or transcription factories [14], whereas transcriptionally inactive regions may form large heterochromatic foci [15], mega-base (Mbp) size lamin-associated domains [16] or Barr [17] and Polycomb bodies [18].…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Transitions and Knotted Solitons in Stretched Chromatin

Michieletto

Orlandini

Marenduzzo

2017

Preprint

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The spreading and regulation of epigenetic marks on chromosomes is crucial to establish and maintain cellular identity. Nonetheless, the dynamical mechanism leading to the establishment and maintenance of a given, cell-line specific, epigenetic pattern is still poorly understood. In this work we propose, and investigate in silico, a possible experimental strategy to illuminate the interplay between 3D chromatin structure and epigenetic dynamics. We consider a set-up where a reconstituted chromatin fibre is stretched at its two ends (e.g., by laser tweezers), while epigenetic enzymes (writers) and chromatin-binding proteins (readers) are flooded into the system. We show that, by tuning the stretching force and the binding affinity of the readers for chromatin, the fibre undergoes a sharp transition between a stretched, epigenetically disordered, state and a crumpled, epigenetically coherent, one. We further investigate the case in which a knot is tied along the chromatin fibre, and find that the knotted segment enhances local epigenetic order, giving rise to "epigenetic solitons" which travel and diffuse along chromatin. Our results point to an intriguing coupling between 3D chromatin topology and epigenetic dynamics, which may be investigated via single molecule experiments.

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Complex multi-enhancer contacts captured by genome architecture mapping

Cited by 614 publications

References 64 publications

Cohesin Loss Eliminates All Loop Domains

Cohesin Loss Eliminates All Loop Domains

Transcription organizes euchromatin similar to an active microemulsion

Epigenetic Transitions and Knotted Solitons in Stretched Chromatin

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