Abstract

In rat fast skeletal muscle, two light chain myosin proteins, LC1 and LC3, are expressed from a single genetic unit. The unique structures of the LC1 and LC3 proteins are generated by differential transcription from two promoters separated by 10kb, accompanied by two alternate splicing pathways. In fetal muscle development, and in differentiating myogenic tissue culture cells, accumulation of the LC1 mRNA precedes that of LC3, suggesting that differential transcription and splicing of LC1 and LC3 messages is developmentally regulated. Our objective is to characterize the mechanisms by which differentiating muscle tissue generates two different myosin light chain transcripts from the same genetic locus. By testing isolated LC1 and LC3 promoters in available tissue culture systems for the ability to express heterologous test genes upon cellular differentiation, we will determine the extent to which upstream regulatory elements play a role in the selective transcription of LC1 and LC3 mRNAs during the differentiation process.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR041926-10
Application #
2081112
Study Section
Molecular Cytology Study Section (CTY)
Project Start
1993-02-01
Project End
1997-01-31
Budget Start
1995-02-01
Budget End
1996-01-31
Support Year
10
Fiscal Year
1995
Total Cost
Indirect Cost

  Institution

Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199

  Publications

Jiang, Ping; Song, Jihwan; Gu, Guoqing et al. (2002) Targeted deletion of the MLC1f/3f downstream enhancer results in precocious MLC expression and mesoderm ablation. Dev Biol 243:281-93
Ceccarelli, E; McGrew, M J; Nguyen, T et al. (1999) An E box comprises a positional sensor for regional differences in skeletal muscle gene expression and methylation. Dev Biol 213:217-29
Houghton, L; Rosenthal, N (1999) Regulation of a muscle-specific transgene by persistent expression of Hox genes in postnatal murine limb muscle. Dev Dyn 216:385-97
Moss, J B; Xavier-Neto, J; Shapiro, M D et al. (1998) Dynamic patterns of retinoic acid synthesis and response in the developing mammalian heart. Dev Biol 199:55-71
Gong, X; Kaushal, S; Ceccarelli, E et al. (1997) Developmental regulation of Zbu1, a DNA-binding member of the SWI2/SNF2 family. Dev Biol 183:166-82
McGrew, M J; Bogdanova, N; Hasegawa, K et al. (1996) Distinct gene expression patterns in skeletal and cardiac muscle are dependent on common regulatory sequences in the MLC1/3 locus. Mol Cell Biol 16:4524-34
Moss, J B; Price, A L; Raz, E et al. (1996) Green fluorescent protein marks skeletal muscle in murine cell lines and zebrafish. Gene 173:89-98
Engert, J C; Servaes, S; Sutrave, P et al. (1995) Activation of a muscle-specific enhancer by the Ski proto-oncogene. Nucleic Acids Res 23:2988-94
Xiao, Y; Grieshammer, U; Rosenthal, N (1995) Regulation of a muscle-specific transgene by retinoic acid. J Cell Biol 129:1345-54
Grieshammer, U; McGrew, M J; Rosenthal, N (1995) Role of methylation in maintenance of positionally restricted transgene expression in developing muscle. Development 121:2245-53

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