The SET oncoprotein promotes estrogen-induced transcription by facilitating establishment of active chromatin

Document Type

Article

Publication Date

2-21-2023

Abstract

SET is a multifunctional histone-binding oncoprotein that regulates transcription by an unclear mechanism. Here we show that SET enhances estrogen-dependent transcription. SET knockdown abrogates transcription of estrogen-responsive genes and their enhancer RNAs. In response to 17β-estradiol (E2), SET binds to the estrogen receptor α (ERα) and is recruited to ERα-bound enhancers and promoters at estrogen response elements (EREs). SET functions as a histone H2 chaperone that dynamically associates with H2A.Z via its acidic C-terminal domain and promotes H2A.Z incorporation, ERα, MLL1, and KDM3A loading and modulates histone methylation at EREs. SET depletion diminishes recruitment of condensin complexes to EREs and impairs E2-dependent enhancer-promoter looping. Thus, SET boosts E2-induced gene expression by establishing an active chromatin structure at ERα-bound enhancers and promoters, which is essential for transcriptional activation.

Identifier

85148250353 (Scopus)

Publication Title

Proceedings of the National Academy of Sciences of the United States of America

External Full Text Location

https://doi.org/10.1073/pnas.2206878120

e-ISSN

10916490

ISSN

00278424

PubMed ID

36791099

Issue

8

Volume

120

Grant

ACI-1445606

Fund Ref

Sistema Nacional de Investigadores

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