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

Jordán-Pla A, Yu S, Waldholm J, Källman T, Östlund Farrants AK, Visa N

BMC Genomics 19 (1) 367 [2018-05-18; online 2018-05-18]

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. However, recent studies have provided evidence for a non-catalytic function of BRM in the transcriptional regulation of a few specific genes. Here 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. This 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.

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PubMed 29776334

DOI 10.1186/s12864-018-4746-2

Crossref 10.1186/s12864-018-4746-2

pii: 10.1186/s12864-018-4746-2
pmc: PMC5960078
GEO: GSE95236 The distribution of Brahma in the genome of Drosophila melanogaster S2 cells and the roles of Brahma in transcription and pre-mRNA processin