Enhancer Switching in Cell Lineage Priming Is Linked to eRNA, Brg1’s AT-Hook, and SWI/SNF Recruitment

Authors

Dhurjhoti Saha
Srinivas Animireddy
Junwoo Lee
Anna Thommen
McKenzie M Murvin
Yue Lu
J Mauro Calabrese
Blaine Bartholomew

Publication Date

5-16-2024

Journal

Molecular Cell

DOI

10.1016/j.molcel.2024.03.013

PMID

38593804

PMCID

PMC11104297

PubMedCentral® Posted Date

5-16-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

RNA transcribed from enhancers, i.e., eRNA, has been suggested to directly activate transcription by recruiting transcription factors and co-activators. Although there have been specific examples of eRNA functioning in this way, it is not clear how general this may be. We find that the AT-hook of SWI/SNF preferentially binds RNA and, as part of the esBAF complex, associates with eRNA transcribed from intronic and intergenic regions. Our data suggest that SWI/SNF is globally recruited in cis by eRNA to cell-type-specific enhancers, representative of two distinct stages that mimic early mammalian development, and not at enhancers that are shared between the two stages. In this manner, SWI/SNF facilitates recruitment and/or activation of MLL3/4, p300/CBP, and Mediator to stage-specific enhancers and super-enhancers that regulate the transcription of metabolic and cell lineage priming-related genes. These findings highlight a connection between ATP-dependent chromatin remodeling and eRNA in cell identity and typical- and super-enhancer activation.

Keywords

Animals, Humans, Cell Lineage, Chromatin Assembly and Disassembly, Chromosomal Proteins, Non-Histone, DNA Helicases, Enhancer Elements, Genetic, Nuclear Proteins, Transcription Factors, SWI/SNF, eRNA, Brg1/Smarca4, naïve, primed, EpiSCs, enhancer, MLL3/4, Mediator (Med1), p300/CBP, RNAPII

Published Open-Access

yes

Recommended Citation

Saha, Dhurjhoti; Animireddy, Srinivas; Lee, Junwoo; et al., "Enhancer Switching in Cell Lineage Priming Is Linked to eRNA, Brg1’s AT-Hook, and SWI/SNF Recruitment" (2024). Faculty, Staff and Student Publications. 4239.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4239