Transcription Factor Occupancy in Differentiating Skeletal Muscle

Author: Kirilusha, Anthony George

Year: 2014

Degree: Dissertation (Ph.D.)

Advisor: Wold, Barbara J.

Committee Members: Stathopoulos, Angelike; Sternberg, Paul W.; Rothenberg, Ellen V.; Mjolsness, Eric D.; Wold, Barbara J.

Option: Biology

DOI: 10.7907/4Q24-CJ96

Abstract

With recent advances in high-throughput sequencing, mapping of genome-wide transcription factor occupancy has become feasible. To advance the understanding of skeletal muscle differentiation specifically and transcriptional regulation in general, I determined the genome-wide occupancy map for myogenin in differentiating C2C12 myocyte cells. I then analyzed the myogenin map for underlying sequence content and the association between occupied elements and expression trajectories of adjacent genes. Having determined that myogenin primarily associates with expressed genes, I performed a similar analysis on occupancy maps of other transcription factors active during skeletal muscle differentiation, including an extensive analysis of co-occupancy. This analysis provided strong motif evidence for protein-protein interactions as the primary driving force in the formation of Myogenin / Mef2 and MyoD / AP-1 complexes at jointly-occupied sites. Finally, factor occupancy analysis was extended to include bHLH transcription factors in tissues other than skeletal muscle. The cross-tissue analysis led to the emergence of a motif structure used by bHLH TFs to encode either tissue-specific or "general" (public) access in a variety of lineages.

Files