Cohesin-Dependent and -Independent Mechanisms Mediate Chromosomal Contacts between Promoters and Enhancers.

Cell Reports
Michiel J. ThieckeMikhail Spivakov

Abstract

It is currently assumed that 3D chromosomal organization plays a central role in transcriptional control. However, depletion of cohesin and CTCF affects the steady-state levels of only a minority of transcripts. Here, we use high-resolution Capture Hi-C to interrogate the dynamics of chromosomal contacts of all annotated human gene promoters upon degradation of cohesin and CTCF. We show that a majority of promoter-anchored contacts are lost in these conditions, but many contacts with distinct properties are maintained, and some new ones are gained. The rewiring of contacts between promoters and active enhancers upon cohesin degradation associates with rapid changes in target gene transcription as detected by SLAM sequencing (SLAM-seq). These results provide a mechanistic explanation for the limited, but consistent, effects of cohesin and CTCF depletion on steady-state transcription and suggest the existence of both cohesin-dependent and -independent mechanisms of enhancer-promoter pairing.

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Aug 14, 2020·Cell Cycle·Dafne Campigli Di GiammartinoEffie Apostolou
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Datasets Mentioned

BETA
GSE145736

Methods Mentioned

BETA
Hi-C
Capture Hi-C
Promoter Capture Hi-C
ChIP-seq
immunoprecipitation
ChIP
RNA-seq
Transfection
flow cytometry
PC-HiC

Key Resources (RRID) Mentioned

AB_304749
AB_449369
AB_477579

Software Mentioned

nnet R
car R
Cluster Flow
HOMER
MASS
Chicdiff
SLAM
LAGO
LASSO
glmnet R

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