A New Serum-responsive, Cardiac Tissue-specific Transcription Factor That Recognizes the MEF-2 Site in the Myosin Light Chain-2 Promoter

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 1993 Feb 1

PMID 8423788

Citations 9

Authors

M D Zhou

S K Goswami

M E Martin

M A Siddiqui

Affiliations

Soon will be listed here.

Abstract

We have identified a serum-responsive, cardiac tissue-specific transcription factor, BBF-1, that recognizes an AT-rich sequence (element B), identical to the myocyte enhancer factor (MEF-2) target site, in the cardiac myosin light chain-2 (MLC-2) promoter. Deletion of the element B sequence alone from the cardiac MLC-2 promoter causes, as does that of the MEF-2 site from other promoters and the enhancer of skeletal muscle genes, a marked reduction of transcription. BBF-1 is distinguishable from cardiac MEF-2 on the basis of immunoprecipitation with an antibody which recognizes MEF-2 but not BBF-1. Unlike MEF-2, BBF-1 is present exclusively in nuclear extracts from cardiac muscle cells cultured in a medium containing a high concentration of serum. Removal of serum from culture medium abolishes BBF-1 activity selectively with a concomitant loss of the positive regulatory effect of element B on MLC-2 gene transcription, indicating that there is a correlation between the BBF-1 binding activity and the tissue-specific role of the element B (MEF-2 site) sequence. The loss of element B-mediated activation of transcription is reversed following the refeeding of cells with serum-containing medium. These data demonstrate that cardiac muscle cells contain two distinct protein factors, MEF-2 and BBF-1, which bind to the same target site but that, unlike MEF-2, BBF-1 is serum inducible and cardiac tissue specific. BBF-1 thus appears to be a crucial member of the MEF-2 family of proteins which will serve as an important tool in understanding the regulatory mechanism(s) underlying cardiogenic differentiation.

Citing Articles

Repression of the cardiac myosin light chain-2 gene in skeletal muscle requires site-specific association of antithetic regulator, Nished, and HDACs.

Mathew S, Galatioto J, Mascareno E, Siddiqui M J Cell Mol Med. 2009; 13(8B):1952-1961.

PMID: 19604314 PMC: 4940774. DOI: 10.1111/j.1582-4934.2008.00525.x.

Modulation of MLC-2v gene expression by AP-1: complex regulatory role of Jun in cardiac myocytes.

Goswami S, Shafiq S, Siddiqui M Mol Cell Biochem. 2001; 217(1-2):13-20.

PMID: 11269656 DOI: 10.1023/a:1007296330181.

Signal transduction and transcriptional adaptation in embryonic heart development and during myocardial hypertrophy.

Ghatpande S, Goswami S, Mascareno E, Siddiqui M Mol Cell Biochem. 1999; 196(1-2):93-7.

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A muscle-specific enhancer within intron 1 of the human dystrophin gene is functionally dependent on single MEF-1/E box and MEF-2/AT-rich sequence motifs.

Klamut H, Worton R, Ray P Nucleic Acids Res. 1997; 25(8):1618-25.

PMID: 9092671 PMC: 146611. DOI: 10.1093/nar/25.8.1618.

The MEF-3 motif is required for MEF-2-mediated skeletal muscle-specific induction of the rat aldolase A gene.

Hidaka K, Yamamoto I, Arai Y, Mukai T Mol Cell Biol. 1993; 13(10):6469-78.

PMID: 8413246 PMC: 364706. DOI: 10.1128/mcb.13.10.6469-6478.1993.

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