WAPL maintains a cohesin loading cycle to preserve cell-type-specific distal gene regulation

Liu, Ning Qing; Maresca, Michela; Brand, Teun van den; Braccioli, Luca; Schijns, Marijne M.G.A.; Teunissen, Hans; Bruneau, Benoit G.; Nora, Elphège P.; Wit, Elzo de

doi:10.1038/s41588-020-00744-4

Cited by 126 publications

(157 citation statements)

References 73 publications

Supporting

Mentioning

141

Contrasting

Order By: Relevance

“…This could be mediated by an increase in their interaction frequency through the process of loop extrusion or result from direct bridging of enhancers and promoters by cohesin. These findings are consistent with a recently reported role of the cohesin release factor WAPL in regulating gene expression 40 and a potential role of cohesin movement along the chromatin in directing regulatory factors, as suggested in a recent preprint 41 . Of interest, it has been suggested that cohesin might be particularly important for mediating very long-range interactions between enhancers and promoters 24,42 .…”

Section: Mainsupporting

confidence: 92%

Analysis of sub-kilobase chromatin topology reveals nano-scale regulatory interactions with variable dependence on cohesin and CTCF

Aljahani

Hua

Karpinska

et al. 2021

Preprint

View full text Add to dashboard Cite

Enhancers and promoters predominantly interact within large-scale topologically associating domains (TADs), which are formed by loop extrusion mediated by cohesin and CTCF. However, it is unclear whether complex chromatin structures exist at sub-kilobase-scale and to what extent fine-scale regulatory interactions depend on loop extrusion. To address these questions, we present an MNase-based chromosome conformation capture (3C) approach, which has enabled us to generate the most detailed local interaction data to date and precisely investigate the effects of cohesin and CTCF depletion on chromatin architecture. Our data reveal that cis-regulatory elements have distinct internal nano-scale structures, within which local insulation is dependent on CTCF, but which are independent of cohesin. In contrast, we find that depletion of cohesin causes a subtle reduction in longer-range enhancer-promoter interactions and that CTCF depletion can cause rewiring of regulatory contacts. Together, our data show that loop extrusion is not essential for enhancer-promoter interactions, but contributes to their robustness and specificity and to precise regulation of gene expression.

show abstract

Section: Mainsupporting

confidence: 92%

Analysis of sub-kilobase chromatin topology reveals nano-scale regulatory interactions with variable dependence on cohesin and CTCF

Aljahani

Hua

Karpinska

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…One possibility is that the dynamic and low-affinity BRG1-cohesin interaction may be important for keeping a pool of dynamic cohesin. Cohesin dynamics have been shown to be important for their function in mediating E-P interactions ( Kueng et al, 2006 ; Liu et al, 2021 ). The reduced interactions with BRG1 upon depolarization may increase cohesin dynamics and change cohesin binding to E-P regions.…”

Section: Discussionmentioning

confidence: 99%

Neuronal activity-induced BRG1 phosphorylation regulates enhancer activation

et al. 2021

View full text Add to dashboard Cite

SUMMARY Neuronal activity-induced enhancers drive gene activation. We demonstrate that BRG1, the core subunit of SWI/SNF-like BAF ATP-dependent chromatin remodeling complexes, regulates neuronal activity-induced enhancers. Upon stimulation, BRG1 is recruited to enhancers in an H3K27Ac-dependent manner. BRG1 regulates enhancer basal activities and inducibility by affecting cohesin binding, enhancer-promoter looping, RNA polymerase II recruitment, and enhancer RNA expression. We identify a serine phosphorylation site in BRG1 that is induced by neuronal stimulations and is sensitive to CaMKII inhibition. BRG1 phosphorylation affects its interaction with several transcription co-factors, including the NuRD repressor complex and cohesin, possibly modulating BRG1-mediated transcription outcomes. Using mice with knockin mutations, we show that non-phosphorylatable BRG1 fails to efficiently induce activity-dependent genes, whereas phosphomimic BRG1 increases enhancer activity and inducibility. These mutant mice display anxiety-like phenotypes and altered responses to stress. Therefore, we reveal a mechanism connecting neuronal signaling to enhancer activities through BRG1 phosphorylation.

show abstract

“…2f ). We therefore conducted spike-in calibrated ChIP-Seq to precisely quantify epigenomic changes (see Methods 17 , Extended Data Fig. 4a ).…”

Section: Mainmentioning

confidence: 99%

SARS-CoV-2 Restructures the Host Chromatin Architecture

Wang

Lee

Xiong

et al. 2021

Preprint

View full text Add to dashboard Cite

SARS-CoV-2 has made >190-million infections worldwide, thus it is pivotal to understand the viral impacts on host cells. Many viruses can significantly alter host chromatin, but such roles of SARS-CoV-2 are largely unknown. Here, we characterized the three-dimensional (3D) genome architecture and epigenome landscapes in human cells after SARS-CoV-2 infection, revealing remarkable restructuring of host chromatin architecture. High-resolution Hi-C 3.0 uncovered widespread A compartmental weakening and A-B mixing, together with a global reduction of intra-TAD chromatin contacts. The cohesin complex, a central organizer of the 3D genome, was significantly depleted from intra-TAD regions, supporting that SARS-CoV-2 disrupts cohesin loop extrusion. Calibrated ChIP-Seq verified chromatin restructuring by SARS-CoV-2 that is particularly manifested by a pervasive reduction of euchromatin modifications. Built on the rewired 3D genome/epigenome maps, a modified activity-by-contact model highlights the transcriptional weakening of antiviral interferon response genes or virus sensors (e.g., DDX58) incurred by SARS-CoV-2. In contrast, pro-inflammatory genes (e.g. IL-6) high in severe infections were uniquely regulated by augmented H3K4me3 at their promoters. These findings illustrate how SARS-CoV-2 rewires host chromatin architecture to confer immunological gene deregulation, laying a foundation to characterize the long-term epigenomic impacts of this virus.

show abstract

WAPL maintains a cohesin loading cycle to preserve cell-type-specific distal gene regulation

Cited by 126 publications

References 73 publications

Analysis of sub-kilobase chromatin topology reveals nano-scale regulatory interactions with variable dependence on cohesin and CTCF

Analysis of sub-kilobase chromatin topology reveals nano-scale regulatory interactions with variable dependence on cohesin and CTCF

Neuronal activity-induced BRG1 phosphorylation regulates enhancer activation

SARS-CoV-2 Restructures the Host Chromatin Architecture

Contact Info

Product

Resources

About