The impact of SWI/SNF and NuRD inactivation on gene expression is tightly coupled with levels of RNA polymerase II occupancy at promoters

Sachin Pundhir*, Jinyu Su, Marta Tapia, Anne Meldgaard Hansen, James Seymour Haile, Klaus Hansen, Bo Torben Porse

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

4 Citations (Scopus)
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Abstract

SWI/SNF and NuRD are protein complexes that antagonistically regulate DNA accessibility. However, repression of their activities often leads to unanticipated changes in target gene expression (paradoxical), highlighting our incomplete understanding of their activities. Here we show that SWI/SNF and NuRD are in a tug-of-war to regulate PRC2 occupancy at lowly expressed and bivalent genes in mouse embryonic stem cells (mESCs). In contrast, at promoters of average or highly expressed genes, SWI/SNF and NuRD antagonistically modulate RNA polymerase II (Pol II) release kinetics, arguably owing to accompanying alterations in H3.3 and H2A.Z levels at promoter-flanking nucleosomes, leading to paradoxical changes in gene expression. Owing to this mechanism, the relative activities of the two remodelers potentiate gene promoters toward Pol II–dependent open or PRC2-dependent closed chromatin states. Our results highlight RNA Pol II occupancy as the key parameter in determining the direction of gene expression changes in response to SWI/SNF and NuRD inactivation at gene promoters in mESCs.

Original languageEnglish
JournalGenome Research
Volume33
Issue number3
Pages (from-to)332-345
Number of pages14
ISSN1088-9051
DOIs
Publication statusPublished - 2023

Bibliographical note

Publisher Copyright:
© 2023 Pundhir et al.; Published by Cold Spring Harbor Laboratory Press.

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