Preservation of Chromatin Organization after Acute Loss of CTCF in Mouse Embryonic Stem Cells

Kubo, Naoki; Ishii, Haruhiko; Gorkin, David U.; Meitinger, Franz; Xiong, Xunhao; Fang, Rongxin; T, Liu; Z, Ye; B, Li; Dixon,; Desai, Anal; Zhao, Huimin; Ren, B

doi:10.1101/118737

Cited by 41 publications

(39 citation statements)

References 82 publications

(32 reference statements)

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“…Prolonged or acute depletion of CTCF leads to increased cross-TAD boundary contacts and varying degrees of reduction in TAD boundary insulation (Zuin et al 2014;Kubo et al 2017;Nora et al 2017). This is consistent with CTCF-dependent and -independent mechanisms of boundary formation.…”

Section: Bets As Insulator/architectural Proteinssupporting

confidence: 71%

The Role of Bromodomain and Extraterminal Motif (BET) Proteins in Chromatin Structure

Hsu

Blobel

2017

Cold Spring Harb Symp Quant Biol

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Bromodomain and extraterminal motif (BET) proteins have been widely investigated for their roles in gene regulation and their potential as therapeutic targets in cancer. Pharmacologic BET inhibitors target the conserved bromodomain-acetyllysine interaction and do not distinguish between BRD2, BRD3, and BRD4. Thus, comparatively little is known regarding the distinct roles played by individual family members, as well as the underlying mechanisms that drive the transcriptional effects of BET inhibitors. Here we review studies regarding the contributions of BET proteins to genome structure and function, including recent work identifying a role for BRD2 as a component of functional and physical chromatin domain boundaries. We also discuss directions of future studies aimed at providing insights into broader architectural functions of BET proteins and their roles in chromatin domain boundary formation.

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Section: Bets As Insulator/architectural Proteinssupporting

confidence: 71%

The Role of Bromodomain and Extraterminal Motif (BET) Proteins in Chromatin Structure

Hsu

Blobel

2017

Cold Spring Harb Symp Quant Biol

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“…Cohesin, CTCF and WAPL, but not PDS5 proteins, have also been inactivated in other recent Hi‐C studies which were deposited on bioRxiv (Kubo et al , ) or published in peer‐reviewed journals during preparation or after submission of our manuscript (Gassler et al , ; Haarhuis et al , ; Rao et al , 2017; Schwarzer et al , ). We compare and contrast the results of these as well as the earlier studies (Seitan et al , ; Sofueva et al , ; Zuin et al , ) with ours in the Discussion.…”

Section: Introductionmentioning

confidence: 73%

Topologically associating domains and chromatin loops depend on cohesin and are regulated by CTCF, WAPL, and PDS5 proteins

et al. 2017

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Mammalian genomes are spatially organized into compartments, topologically associating domains (TADs), and loops to facilitate gene regulation and other chromosomal functions. How compartments, TADs, and loops are generated is unknown. It has been proposed that cohesin forms TADs and loops by extruding chromatin loops until it encounters CTCF, but direct evidence for this hypothesis is missing. Here, we show that cohesin suppresses compartments but is required for TADs and loops, that CTCF defines their boundaries, and that the cohesin unloading factor WAPL and its PDS5 binding partners control the length of loops. In the absence of WAPL and PDS5 proteins, cohesin forms extended loops, presumably by passing CTCF sites, accumulates in axial chromosomal positions (vermicelli), and condenses chromosomes. Unexpectedly, PDS5 proteins are also required for boundary function. These results show that cohesin has an essential genome-wide function in mediating long-range chromatin interactions and support the hypothesis that cohesin creates these by loop extrusion, until it is delayed by CTCF in a manner dependent on PDS5 proteins, or until it is released from DNA by WAPL.

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“…This supports the idea that TADs, which are in part formed by these compartmental domains, should be different when comparing cell types with distinct transcription patterns. Recently published studies have examined the role of CTCF in the formation of loops and TADs using an auxin-mediated degradation system in mammals (Kubo et al, 2017; Nora et al, 2017). The loss of CTCF domains and maintenance of compartments seen after CTCF degradation fits with our model.…”

Section: Discussionmentioning

confidence: 99%

Evolutionarily Conserved Principles Predict 3D Chromatin Organization

et al. 2017

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SUMMARY TADs, CTCF loop domains, and A/B compartments have been identified as important structural and functional components of 3D chromatin organization, yet the relationship between these features is not well understood. Using high-resolution Hi-C and HiChIP we show that Drosophila chromatin is organized into domains we term compartmental domains that correspond precisely with A/B compartments at high resolution. We find that transcriptional state is a major predictor of Hi-C contact maps in several eukaryotes tested, including C. elegans and A. thaliana. Architectural proteins insulate compartmental domains by reducing interaction frequencies between neighboring regions in Drosophila, but CTCF loops do not play a distinct role in this organism. In mammals, compartmental domains exist alongside CTCF loop domains to form topological domains. The results suggest that compartmental domains are responsible for domain structure in all eukaryotes, with CTCF playing an important role in domain formation in mammals.

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Preservation of Chromatin Organization after Acute Loss of CTCF in Mouse Embryonic Stem Cells

Abstract: Summary: 26 27The CCCTC-binding factor (CTCF) is widely regarded as a key player in chromosome 28

Cited by 41 publications

References 82 publications

The Role of Bromodomain and Extraterminal Motif (BET) Proteins in Chromatin Structure

The Role of Bromodomain and Extraterminal Motif (BET) Proteins in Chromatin Structure

Topologically associating domains and chromatin loops depend on cohesin and are regulated by CTCF, WAPL, and PDS5 proteins

Evolutionarily Conserved Principles Predict 3D Chromatin Organization

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