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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

1993; Taylor & Francis; Volume: 13; Issue: 7 Linguagem: Inglês

10.1128/mcb.13.7.4432-4444.1993

1098-5549

Hong Zhu, Van Trung Nguyen, Anne B. Brown, Atossa Pourhosseini, Arnold Garcia, Marc van Bilsen, Kenneth R. Chien,

Cardiomyopathy and Myosin Studies

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.