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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
9R01AG008920-04
Application #
3120704
Study Section
Molecular Cytology Study Section (CTY)
Project Start
1985-08-01
Project End
1992-07-31
Budget Start
1989-08-01
Budget End
1990-07-31
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Boston University
Department
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Engert, J C; Berglund, E B; Rosenthal, N (1996) Proliferation precedes differentiation in IGF-I-stimulated myogenesis. J Cell Biol 135:431-40
Rosen, K M; Wentworth, B M; Rosenthal, N et al. (1993) Specific, temporally regulated expression of the insulin-like growth factor II gene during muscle cell differentiation. Endocrinology 133:474-81
Grieshammer, U; Sassoon, D; Rosenthal, N (1992) A transgene target for positional regulators marks early rostrocaudal specification of myogenic lineages. Cell 69:79-93
Wentworth, B M; Donoghue, M; Engert, J C et al. (1991) Paired MyoD-binding sites regulate myosin light chain gene expression. Proc Natl Acad Sci U S A 88:1242-6