A novel, tissue-restricted zinc finger protein (HF-1b) binds to the cardiac regulatory element (HF-1b/MEF-2) in the rat myosin light-chain 2 gene.
The AT-rich element MEF-2 plays an important role in the maintenance of the muscle-specific expression of a number of cardiac and skeletal muscle genes. In the MLC-2 gene, an AT-rich element (HF-1b) which contains a consensus MEF-2 site is required for cardiac tissue-specific expression. The present study reports the isolation and characterization of a cDNA which encodes a novel C2H2 zinc finger (HF-1b) that binds in a sequence-specific manner to the HF-1b/MEF-2 site in the MLC-2 promoter. A number of independent criteria suggest that this HF-1b zinc finger protein is a component of the endogenous HF-1b/MEF-2 binding activity in cardiac muscle cells and that it can serve as a transcriptional activator of the MLC-2 promoter in transient assays. These studies suggest that, in addition to the previously reported RSRF proteins, structurally divergent transcriptional factors can bind to MEF-2-like sites in muscle promoters. These results underscore the complexity of the regulation of the muscle gene program via these AT-rich elements in cardiac and skeletal muscle.
Zhu
H
H
Department of Medicine, University of California, San Diego, School of Medicine, La Jolla 92093.
Nguyen
V T
VT
Brown
A B
AB
Pourhosseini
A
A
Garcia
A V
AV
van Bilsen
M
M
Chien
K R
KR
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism; D003402:Creatine Kinase / Q000235:genetics / Q000378:metabolism; D004247:DNA; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D064326:MEF2 Transcription Factors; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D018006:Myogenic Regulatory Factors; D009218:Myosins / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics; D011401:Promoter Regions, Genetic; D051381:Rats; D051706:Sp4 Transcription Factor; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; D051706:Sp4 Transcription Factor; C081928:Sp4 protein, rat; D014157:Transcription Factors; D004247:DNA; D003402:Creatine Kinase; D009218:Myosins