Metal Regulatory Transcription Factor 1 (MTF1) Interacts with SWI/SNF Chromatin Remodelers to Promote Myogenesis

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Live Poster Session: Zoom Link
Thursday, July 30th 1:15-2:30pm EDT

Julia Kan
Julia Kan

Julia Kan is a rising junior (’22) hailing from Lexington, Massachusetts where she graduated from Lexington High School in 2018. She is double majoring in MB&B and Art Studio with a concentration in Drawing. Julia has been a member of the Padilla-Benavides lab since Spring 2020 and is interested in the roles of transition metals in HeLa cells. Outside of the lab, she is very involved in the campus music scene, and can frequently be found in the CFA playing violin in the Wesleyan Orchestra, playing for a theater show, or singing with her co-ed a cappella group, Notably Sharp. She loves visual art and music and is passionate about finding ways in which the sciences and arts intersect. After Wesleyan, she hopes to go to medical school and become a doctor.

Abstract: Myogenesis is the biological process that leads to the development of skeletal muscle from embryonic stages throughout post-natal growth. Differentiation of myoblasts to skeletal muscle cells is governed by a multitude of myogenic factors and transcriptional regulators. Metal-regulatory transcription factor 1 (MTF1) is a conserved metal-binding transcription factor involved in the maintenance of metal and redox homeostasis. Recently, our lab demonstrated that MTF1 and copper contribute to the expression of several myogenic genes in differentiating primary myoblasts. MTF1 is essential for myoblasts as deletion of this factor leads to apoptosis. MTF1 binds to the promoter regions of several myogenic genes, and copper supplementation stimulates this process. Transcriptional regulation of myogenic genes is achieved by the orchestrated activity of various components of transcriptional machinery. Thus, we hypothesized that MTF1 may interact with additional transcriptional regulators, such as chromatin remodelers, to promote myogenic gene expression, as well as metalloenzymes and metal homeostasis genes. The mammalian SWI/SNF (SWItch/Sucrose Non-Fermentable) chromatin remodeler complex utilizes energy from ATP hydrolysis to modify nucleosome structure. The ATPase BRG1 is the catalytic subunit, essential for proliferation and differentiation of myoblasts. Preliminary data using an unbiased approach of immunoprecipitation coupled to mass spectrometry showed that MTF1 interacts with BRG1 and other SWI/SNF subunits. Here, we performed a preliminary bioinformatic analysis to identify loci that are potentially regulated by MTF1 and BRG1. We compared our published MTF1 ChIP-Seq with publicly available RNA-Seq datasets for differentiated myoblasts lacking Brg1. We found that MTF1-bound to myogenic and cuproenzyme genes required for muscle development correlated with a decreased expression of these genes in the Brg1 depleted myoblasts. Interestingly, no correlation was found with genes involved in metal homeostasis. This data suggests a potential mechanism where MTF1 and SWI/SNF act cooperatively to promote myogenesis, which is independent to maintenance of metal homeostasis.s et aliquam nulla.

Kan-Poster-Summer-2020-FINAL-Julia-Kan

Live Poster Session: Zoom Link
Thursday, July 30th 1:15-2:30pm EDT

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