The myogenic bHLH protein MyoD can initiate muscle gene expression in most primary cell types and non-transformed cell lines. However, MyoD is unable to initiate such expression in many tumor cell lines. It is thus believed that multiple factors must work with the myogenic factor to turn on gene transcription as mediated by MyoD and one or more of these factors is commonly inactivated during tumor formation in various cell lineages. Two novel domains of MyoD have been characterized that are necessary to initiate transcription of endogenous genes and several proteins capable of interacting with one of these domains (C/H) have been identified using the yeast two hybrid approach. The hypotheses of this proposal are that (1) these two domains of MyoD are necessary to establish the myogenic lineage by facilitating the initiation of gene transcription in native chromatin and (2) these domains recruit factors that work with MyoD as a chromatin remodeling complex.
The specific aims of the proposal are to (1) to further characterize the C/H and Box 2 domains in terms of their role in myogenic lineage determination and muscle cell differentiation, (2) functionally characterize factors that interact with these domains, and (3) develop an in vitro chromatin remodeling assay for MyoD and its associated factors.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR045113-02
Application #
2871621
Study Section
Molecular Cytology Study Section (CTY)
Program Officer
Lymn, Richard W
Project Start
1998-05-01
Project End
2003-01-31
Budget Start
1999-02-01
Budget End
2000-01-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
075524595
City
Seattle
State
WA
Country
United States
Zip Code
98109
Conerly, Melissa L; Yao, Zizhen; Zhong, Jun Wen et al. (2016) Distinct Activities of Myf5 and MyoD Indicate Separate Roles in Skeletal Muscle Lineage Specification and Differentiation. Dev Cell 36:375-85
Fong, Abraham P; Yao, Zizhen; Zhong, Jun Wen et al. (2015) Conversion of MyoD to a neurogenic factor: binding site specificity determines lineage. Cell Rep 10:1937-46
Yang, Z J P; Broz, D Kenzelmann; Noderer, W L et al. (2015) p53 suppresses muscle differentiation at the myogenin step in response to genotoxic stress. Cell Death Differ 22:560-73
Yao, Zizhen; Macquarrie, Kyle L; Fong, Abraham P et al. (2014) Discriminative motif analysis of high-throughput dataset. Bioinformatics 30:775-83
Yao, Zizhen; Farr 3rd, Gist H; Tapscott, Stephen J et al. (2013) Pbx and Prdm1a transcription factors differentially regulate subsets of the fast skeletal muscle program in zebrafish. Biol Open 2:546-55
Diede, Scott J; Yao, Zizhen; Keyes, C Chip et al. (2013) Fundamental differences in promoter CpG island DNA hypermethylation between human cancer and genetically engineered mouse models of cancer. Epigenetics 8:1254-60
Dey, Joyoti; Dubuc, Adrian M; Pedro, Kyle D et al. (2013) MyoD is a tumor suppressor gene in medulloblastoma. Cancer Res 73:6828-37
Fong, Abraham P; Tapscott, Stephen J (2013) Skeletal muscle programming and re-programming. Curr Opin Genet Dev 23:568-73
MacQuarrie, Kyle L; Yao, Zizhen; Fong, Abraham P et al. (2013) Comparison of genome-wide binding of MyoD in normal human myogenic cells and rhabdomyosarcomas identifies regional and local suppression of promyogenic transcription factors. Mol Cell Biol 33:773-84
Yao, Zizhen; Fong, Abraham P; Cao, Yi et al. (2013) Comparison of endogenous and overexpressed MyoD shows enhanced binding of physiologically bound sites. Skelet Muscle 3:8

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