Mechanistic Studies of NF-kB Inhibition of Myogenesis

Ohio State University, Columbus OH

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Abstract

[unreadable] DESCRIPTION (provided by applicant): NF-kappaB (NF-kB) is a transcription factor which plays a pivotal role in the regulation of cell growth, differentiation and cellular survival. Accumulating evidence suggest that NF-kB is involved in several skeletal muscle disorders although its mechanism of action is not well defined. In this proposal we attempt to gain insight into the roles of NF-kB in muscle diseases by understanding how NF-kB functions in skeletal myogenesis at a basic level. Recent studies have revealed that NF-kB plays an inhibitory role in skeletal myogenesis through multiple mechanisms. Based on our preliminary results we hypothesized that NF-kB inhibition of myogenesis could occur through direct or indirect repression of troponin gene expression. To test this hypothesis we propose to perform the following aims: 1) determine whether inhibition of troponin gene expression is mediated by direct NF-kB binding; 2) investigate whether NF-kB regulates troponin gene expression indirectly through YY1; 3)perform a genome-wide search of the YY1 and NF-kB target genes. Completion of these aims will provide us new mechnistic insights into how NF-kB function in skeletal myogenesis and advance our understanding of how it participates in the skeletal muscle disorders. [unreadable] [unreadable] [unreadable]