In:
PLOS Genetics, Public Library of Science (PLoS), Vol. 18, No. 11 ( 2022-11-30), p. e1010528-
Abstract:
The relationship between cohesin-mediated chromatin looping and gene expression remains unclear. NIPBL and WAPL are two opposing regulators of cohesin activity; depletion of either is associated with changes in both chromatin folding and transcription across a wide range of cell types. However, a direct comparison of their individual and combined effects on gene expression in the same cell type is lacking. We find that NIPBL or WAPL depletion in human HCT116 cells each alter the expression of ~2,000 genes, with only ~30% of the genes shared between the conditions. We find that clusters of differentially expressed genes within the same topologically associated domain (TAD) show coordinated misexpression, suggesting some genomic domains are especially sensitive to both more or less cohesin. Finally, co-depletion of NIPBL and WAPL restores the majority of gene misexpression as compared to either knockdown alone. A similar set of NIPBL-sensitive genes are rescued following CTCF co-depletion. Together, this indicates that altered transcription due to reduced cohesin activity can be functionally offset by removal of either its negative regulator (WAPL) or the physical barriers (CTCF) that restrict loop-extrusion events.
Type of Medium:
Online Resource
ISSN:
1553-7404
DOI:
10.1371/journal.pgen.1010528
DOI:
10.1371/journal.pgen.1010528.g001
DOI:
10.1371/journal.pgen.1010528.g002
DOI:
10.1371/journal.pgen.1010528.g003
DOI:
10.1371/journal.pgen.1010528.g004
DOI:
10.1371/journal.pgen.1010528.g005
DOI:
10.1371/journal.pgen.1010528.g006
DOI:
10.1371/journal.pgen.1010528.s001
DOI:
10.1371/journal.pgen.1010528.s002
DOI:
10.1371/journal.pgen.1010528.s003
DOI:
10.1371/journal.pgen.1010528.s004
DOI:
10.1371/journal.pgen.1010528.s005
DOI:
10.1371/journal.pgen.1010528.s006
DOI:
10.1371/journal.pgen.1010528.s007
DOI:
10.1371/journal.pgen.1010528.s008
DOI:
10.1371/journal.pgen.1010528.s009
DOI:
10.1371/journal.pgen.1010528.s010
DOI:
10.1371/journal.pgen.1010528.s011
DOI:
10.1371/journal.pgen.1010528.s012
DOI:
10.1371/journal.pgen.1010528.s013
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2186725-2
Permalink