Dynamic relationship of MLL4 and BAF in enhancer activation

Authors

• JC Hargarten
• MJ Vaughan
• OCR Dean
• S Paul
• J Lacks
• PR Williamson

Abstract

Enhancers are cis-regulatory elements that, through working with promoters, control cell type-specific gene expression during differentiation and development. Enhancers are highly regulated by epigenetic factors. We previously reported the inter-dependent roles of the chromatin remodeling complex BRG1/BRM-associated factor (BAF) and histone H3K4 mono-methyltransferase MLL4 (KMT2D) in enhancer activation by the adipogenic transcription factor (TF) C/EBPbÔÅ¢ in preadipocytes. However, the molecular mechanisms by which MLL4 and BAF regulate enhancer activation are not fully understood. Using MyoD-driven myogenesis in preadipocytes, we investigate the dynamic recruitment and actions of MLL4 and BAF at the early steps of enhancer activation upon differentiation induction. To validate our observations, we also utilize the Auxin Inducible Degron (AID) rapid protein degradation system to acutely deplete MLL4 or the inhibition of BRG1, the enzymatic subunit of BAF complex, and assess the effects on enhancers. This project aims to construct a mechanistic model of lineage-determining TF-mediated enhancer activation.

Scientific Focus Area: Chromosome Biology

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