The GBAF chromatin remodeling complex binds H3K27ac and mediates enhancer transcription
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The GBAF chromatin remodeling complex binds H3K27ac and mediates enhancer transcription. / Jefimov, Kirill; Alcaraz, Nicolas; Kloet, Susan L.; Värv, Signe; Sakya, Siri Aastedatter; Vaagenso, Christian; Vermeulen, Michiel; Aasland, Rein; Andersson, Robin.
2018.Research output: Working paper › Preprint › Research
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T1 - The GBAF chromatin remodeling complex binds H3K27ac and mediates enhancer transcription
AU - Jefimov, Kirill
AU - Alcaraz, Nicolas
AU - Kloet, Susan L.
AU - Värv, Signe
AU - Sakya, Siri Aastedatter
AU - Vaagenso, Christian
AU - Vermeulen, Michiel
AU - Aasland, Rein
AU - Andersson, Robin
PY - 2018
Y1 - 2018
N2 - H3K27ac is associated 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. We systematically characterized the composition of GBAF and the conserved GLTSCR1/1L ‘GiBAF’-domain, which we found to be responsible for GBAF complex formation and GLTSCR1L nuclear localization. Inhibition of the bromodomain of BRD9 revealed interaction between GLTSCR1L and H3K27ac to be BRD9-dependent and led to GLTSCR1L dislocation from its preferred binding sites at H3K27ac-associated enhancers. GLTSCR1L disassociation from chromatin resulted in genome-wide downregulation of enhancer transcription while leaving most mRNA expression levels unchanged, except for reduced mRNA levels from loci topologically linked to affected enhancers. Our results indicate that GBAF is an enhancer-associated chromatin remodeler important for transcriptional and regulatory activity of enhancers.
AB - H3K27ac is associated 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. We systematically characterized the composition of GBAF and the conserved GLTSCR1/1L ‘GiBAF’-domain, which we found to be responsible for GBAF complex formation and GLTSCR1L nuclear localization. Inhibition of the bromodomain of BRD9 revealed interaction between GLTSCR1L and H3K27ac to be BRD9-dependent and led to GLTSCR1L dislocation from its preferred binding sites at H3K27ac-associated enhancers. GLTSCR1L disassociation from chromatin resulted in genome-wide downregulation of enhancer transcription while leaving most mRNA expression levels unchanged, except for reduced mRNA levels from loci topologically linked to affected enhancers. Our results indicate that GBAF is an enhancer-associated chromatin remodeler important for transcriptional and regulatory activity of enhancers.
U2 - 10.1101/445148
DO - 10.1101/445148
M3 - Preprint
BT - The GBAF chromatin remodeling complex binds H3K27ac and mediates enhancer transcription
ER -
ID: 355239418