Global and gene-specific analyses show distinct roles for Myod and Myog at a common set of promoters.
Journal: 2006/March - EMBO Journal
ISSN: 0261-4189
Abstract:
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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EMBO J 25(3): 502-511

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

Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Whitehead Institute for Biomedical Research, Cambridge, MA, USA
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA
Broad Institute of MIT and Harvard, Cambridge, MA, USA
Whitehead Institute for Biomedical Research, 9 Cambridge Center, MA 02493, USA. E-mail: ude.tim.iw@gnuoy
Fred Hutchinson Cancer Research Center, Mailstop C3-168, 1100 Fairview Avenue North, Seattle, WA 98109-1024, USA. Tel.: +1 206 667 4499; Fax: +1 206 667 6524; E-mail: gro.crchf@tocspats
These authors contributed equally to this work
Received 2005 Oct 19; Accepted 2005 Dec 21.

Abstract

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.

Keywords: muscle differentiation, Myod, Myogenin, regulatory network
Abstract
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Acknowledgments

We thank DT Odom and the Whitehead Microarray Facility for production of the promoter arrays, the Whitehead Institute Bioinformatics Group and Elizabeth Herbolsheimer for computational support, and J Delrow and the FHCRC Genomics Facility. This work was supported by NIH AR45113 (SJT), NIH CA74841 (CK), and NIH {"type":"entrez-nucleotide","attrs":{"text":"GM069400","term_id":"221363575","term_text":"GM069400"}}GM069400 and {"type":"entrez-nucleotide","attrs":{"text":"HG002668","term_id":"548932704","term_text":"HG002668"}}HG002668 (RAY). YC was supported by an FHCRC Interdisciplinary Training grant sponsored by Amgen and a Fellowship from the Merck Research Laboratories. RMK was supported by an American Cancer Society postdoctoral fellowship and LAB by NRSA postdoctoral fellowship {"type":"entrez-nucleotide","attrs":{"text":"CA094664","term_id":"34947971","term_text":"CA094664"}}CA094664.

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