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A conserved 28-base-pair element (HF-1) in the rat cardiac myosin light-chain-2 gene confers cardiac-specific and alpha-adrenergic-inducible expression in cultured neonatal rat myocardial cells.

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.
AuthorsH Zhu, A V Garcia, R S Ross, S M Evans, K R Chien
JournalMolecular and cellular biology (Mol Cell Biol) Vol. 11 Issue 4 Pg. 2273-81 (Apr 1991) ISSN: 0270-7306 [Print] United States
PMID1848675 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Receptors, Adrenergic, alpha
  • Myosins
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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