PLX242362

GSE121351: A non-canonical GLTSCR1L-containing BAF complex mediates H3K27ac-dependent enhancer activities

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

H3K27ac is known to associate with regulatory active enhancers, but its exact role in enhancer function remains elusive. Using mass spectrometry-based interaction proteomics, we identified the Super Elongation Complex (SEC) and GBAF, a non-canonical GLTSCR1L- and BRD9-containing SWI/SNF chromatin remodeling complex, to be major interactors of H3K27ac. Our interaction proteomics analysis refined the composition of GBAF by adding BCL7A/B/C as a new subunit. We further characterized the conserved GLTSCR1/1L-contained GiBAF-domain, which we found to be responsible for GBAF complex formation and nuclear localization. Inhibition of the bromodomain of BRD9 revealed interaction between GLTSCR1L and BRD9 to be H3K27ac dependent and led to GLTSCR1L dislocation from its preferred binding sites at H3K27ac-associated enhancers. GLTSCR1L disassociation from chromatin resulted in a genome-wide downregulation of enhancer transcription. Our results indicate that GBAF is an enhancer-associated chromatin remodeller important for the correct transcriptional and regulatory activity of enhancers. SOURCE: Nicolas Alcaraz (nalcaraz@binf.ku.dk) - Andersson Lab University of Copenhagen