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Transcription Factor Occupancy in Differentiating Skeletal Muscle


Kirilusha, Anthony George (2014) Transcription Factor Occupancy in Differentiating Skeletal Muscle. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/4Q24-CJ96.


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.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:myogenesis, myogenin, occupancy, transcriptional regulation, skeletal muscle
Degree Grantor:California Institute of Technology
Division:Biology and Biological Engineering
Major Option:Biology
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Wold, Barbara J.
Thesis Committee:
  • Stathopoulos, Angelike (chair)
  • Sternberg, Paul W.
  • Rothenberg, Ellen V.
  • Mjolsness, Eric D.
  • Wold, Barbara J.
Defense Date:27 May 2014
Non-Caltech Author Email:akirilus (AT)
Record Number:CaltechTHESIS:06112014-114426786
Persistent URL:
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:8518
Deposited By: Anthony Kirilusha
Deposited On:18 Jun 2014 16:50
Last Modified:08 Nov 2023 00:36

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