SWI/SNF regulates half of its targets without the need of ATP-driven nucleosome remodeling by Brahma

Antonio Jordán-Pla,Neus Visa,Johan Waldholm,Thomas Källman,Ann-Kristin Östlund Farrants,Simei Yu

doi:10.1186/s12864-018-4746-2

Antonio Jordán-Pla, Neus Visa + Show 4 more

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https://doi.org/10.1186/s12864-018-4746-2

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Journal: BMC Genomics	Publication Date: May 18, 2018
Citations: 20	License type: open-access

Affiliation: Stockholm University, Uppsala University

Abstract

BackgroundBrahma (BRM) is the only catalytic subunit of the SWI/SNF chromatin-remodeling complex of Drosophila melanogaster. The function of SWI/SNF in transcription has long been attributed to its ability to remodel nucleosomes, which requires the ATPase activity of BRM. However, recent studies have provided evidence for a non-catalytic function of BRM in the transcriptional regulation of a few specific genes.ResultsHere we have used RNA-seq and ChIP-seq to identify the BRM target genes in S2 cells, and we have used a catalytically inactive BRM mutant (K804R) that is unable to hydrolyze ATP to investigate the magnitude of the non-catalytic function of BRM in transcription regulation. We show that 49% of the BRM target genes in S2 cells are regulated through mechanisms that do not require BRM to have an ATPase activity. We also show that the catalytic and non-catalytic mechanisms of SWI/SNF regulation operate on two subsets of genes that differ in promoter architecture and are linked to different biological processes.ConclusionsThis study shows that the non-catalytic role of SWI/SNF in transcription regulation is far more prevalent than previously anticipated and that the genes that are regulated by SWI/SNF through ATPase-dependent and ATPase-independent mechanisms have specialized roles in different cellular and developmental processes.

Highlights

Brahma (BRM) is the only catalytic subunit of the SWI/SNF chromatin-remodeling complex of Drosophila melanogaster
The BRM-bound genes in the genome of S2 cells Chromatin immunoprecipitation (ChIP)-seq experiments using an antibody against the endogenous BRM identified 2521 genes bound by BRM in S2 cells of D. melanogaster
The levels of BRM were not correlated with the levels of RNA polymerase II (RNAPII) at individual genes (Additional file 1: Figure S1), in agreement with the fact that many BRM target genes are repressed by BRM

Summary

Introduction

Brahma (BRM) is the only catalytic subunit of the SWI/SNF chromatin-remodeling complex of Drosophila melanogaster. The function of SWI/SNF in transcription has long been attributed to its ability to remodel nucleosomes, which requires the ATPase activity of BRM. Recent studies have provided evidence for a non-catalytic function of BRM in the transcriptional regulation of a few specific genes. SWI/SNF is an evolutionarily conserved ATP-dependent chromatin remodeling complex that controls fundamental biological processes such as progress through the cell cycle, development and metabolism [1, 2]. Brahma (BRM) is the only ATPase subunit of the SWI/ SNF complex of Drosophila melanogaster. The regulation of gene transcription by SWI/SNF has instead been regarded as a process that is intimately associated with the ability of BRM to undergo conformational changes in an ATP-dependent manner.

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