Description:

The Department of Biochemistry and Molecular Genetics Departmental Seminar Series presents:

Xiaomin Bao, PhD
Assistant Professor
Molecular Biosciences
Northwestern University

“Open” and “closed” chromatin states impact gene expression by rendering genomic regions either accessible for expression or by repressing them, respectively. Chromatin remodeling complexes, such as the BAF (SWI/SNF) complex, control the transition between these open and closed states. In human epidermal tissue, several genes encoding BAF subunits are dynamically expressed. However, how BAF complex acts to control tissue homeostasis remains incompletely understood. We identified that the BAF53a/ACTL6a regulatory subunit is highly enriched in epidermal progenitors, and that ACTL6a is essential for maintaining progenitor function in vivo. The BAF catalytic subunits, on the other hand, are required to promote epidermal differentiation. To characterize how BAF controls the chromatin states to promote differentiation, we mapped chromatin accessibility genome-wide in the presence or absence of the BAF catalytic subunits BRG1/BRM using ATAC-seq. We found that BAF is required to maintain accessibility of 11.6% of total open chromatin regions in epidermal differentiation. Motif searches of these BAF-dependent regions identified a striking enrichment of the p63 DNA binding motif. Leveraging ChIP-seq as well as transcriptome profiling, we further demonstrated that BAF and p63 cooperatively bind to maintain open chromatin and promote epidermal differentiation. These data indicate that multiple BAF subunits dynamically regulate the function of BAF chromatin remodeling complex to control human tissue homeostasis.