Abstract |
To study the transcriptional regulatory mechanisms which mediate cardiac-specific and inducible expression during myocardial cell hypertrophy, we have extensively characterized the rat cardiac myosin light-chain-2 (MLC-2) gene as a model system. The MLC-2 gene encodes a relatively abundant contractile protein in slow skeletal and cardiac muscle and is upregulated during in vivo cardiac hypertrophy and alpha- adrenergic-mediated hypertrophy of neonatal rat myocardial cells. In transient expression assays employing a series of MLC-2-luciferase constructs, recent studies have identified a 250-bp fragment which is sufficient for both cardiac-specific and alpha- adrenergic-inducible expression. Within this 250-bp fragment lie three regions (HF-1, HF-2, and HF-3), each greater than 10 bp in length, which are conserved between the chicken and rat cardiac MLC-2 genes, suggesting their potential role in the regulated expression of this contractile protein gene. As assessed by substitution mutations within each of the conserved regions, the present study demonstrates that HF-1 and HF-2 are important in both cardiac-specific and inducible expression, while HF-3 has no detectable role in the regulated expression of the MLC-2 gene in transient expression assays. HF-1 sequences confer both cardiac-specific and inducible expression to a neutral promoter- luciferase construct but have no significant effect in the skeletal muscle or nonmuscle cell contexts. Thus, these studies have identified a new cardiac-specific regulatory element (HF-1) which plays a role in both cardiac-specific and inducible expression during myocardial cell hypertrophy.
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Authors | H Zhu, A V Garcia, R S Ross, S M Evans, K R Chien |
Journal | Molecular and cellular biology
(Mol Cell Biol)
Vol. 11
Issue 4
Pg. 2273-81
(Apr 1991)
ISSN: 0270-7306 [Print] United States |
PMID | 1848675
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Receptors, Adrenergic, alpha
- Myosins
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Topics |
- Animals
- Animals, Newborn
- Base Composition
- Base Sequence
- Cell Differentiation
- Cells, Cultured
- Gene Expression
- Genes
- Mice
- Molecular Sequence Data
- Muscles
(cytology, metabolism)
- Myocardium
(cytology, metabolism)
- Myosins
(genetics)
- Organ Specificity
(genetics)
- Rats
- Rats, Inbred Strains
- Receptors, Adrenergic, alpha
(metabolism)
- Regulatory Sequences, Nucleic Acid
- Up-Regulation
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