4.8 Article

Global and gene-specific analyses show distinct roles for Myod and Myog at a common set of promoters

Journal

EMBO JOURNAL
Volume 25, Issue 3, Pages 502-511

Publisher

WILEY
DOI: 10.1038/sj.emboj.7600958

Keywords

muscle differentiation; Myod; Myogenin; regulatory network

Funding

  1. NCI NIH HHS [R29 CA074841, CA094664, R01 CA074841, F32 CA094664, CA74841] Funding Source: Medline
  2. NHGRI NIH HHS [R01 HG002668, HG002668, R01 HG002668-03] Funding Source: Medline
  3. NIAMS NIH HHS [R01 AR045113, AR45113] Funding Source: Medline
  4. NIGMS NIH HHS [GM069400, R01 GM069400] Funding Source: Medline

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We used a combination of genome-wide and promoter-specific DNA binding and expression analyses to assess the functional roles of Myod and Myog in regulating the program of skeletal muscle gene expression. Our findings indicate that Myod and Myog have distinct regulatory roles at a similar set of target genes. At genes expressed throughout the program of myogenic differentiation, Myod can bind and recruit histone acetyltransferases. At early targets, Myod is sufficient for near full expression, whereas, at late expressed genes, Myod initiates regional histone modification but is not sufficient for gene expression. At these late genes, Myog does not bind efficiently without Myod; however, transcriptional activation requires the combined activity of Myod and Myog. Therefore, the role of Myog in mediating terminal differentiation is, in part, to enhance expression of a subset of genes previously initiated by Myod.

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