SWI/SNF-dependent genes are defined by their chromatin landscape

Area of Science:

• Chromatin biology
• Gene regulation
• Molecular mechanisms

Background:

• SWI/SNF complexes are ATP-dependent machines that remodel chromatin.
• Understanding their specific roles in gene regulation is essential for deciphering cellular processes.

Purpose of the Study:

• To characterize features of genes dependent on SWI/SNF complexes.
• To investigate the role of SWI/SNF activity in chromatin accessibility and nucleosome occupancy at promoters and enhancers.

Main Methods:

• Utilized BRM014, an inhibitor of SWI/SNF ATPase activity.
• Analyzed chromatin accessibility, nucleosome occupancy, histone marks, and motif enrichment at promoters and regulatory regions.
• Employed machine-learning models to identify determinants of SWI/SNF dependency.

Main Results:

• SWI/SNF activity is vital for maintaining chromatin accessibility and nucleosome occupancy at most enhancers, but not typically at promoters.
• SWI/SNF dependency is observed in genes with low-to-medium expression and specific promoter characteristics (low accessibility, low active marks, high H3K4me1/H3K4me3 ratio, low phasing, TATA-box enrichment).
• These genes are often associated with the Brahma-related gene 1/Brahma-associated factor (BAF) complex, SWI/SNF-dependent enhancers, and encode signal transduction, developmental, or cell identity factors.

Conclusions:

• The chromatin landscape of promoters and surrounding regulatory regions dictates SWI/SNF dependency.
• SWI/SNF complexes play distinct roles in regulating enhancers versus promoters.
• Specific gene types, particularly non-housekeeping genes, rely on SWI/SNF activity for proper expression through defined chromatin features.