Competition between negative acting YY1 versus positive acting serum response factor and tinman homologue Nkx-2.5 regulates cardiac alpha-actin promoter activity

Molecular Endocrinology
C Y Chen, R J Schwartz

Abstract

Transcription of sarcomeric alpha-actin genes is developmentally regulated during skeletal and cardiac muscle development through fine-tuned control mechanisms involving multiple cooperative and antagonistic transcription factors. Among the cis-acting DNA elements recognized by these factors is the sequence CC(A/T)6GG of the serum response element (SRE), which is present in a number of growth factor-inducible and myogenic specified genes. We recently showed that the cardiogenic homeodomain factor, Nkx-2.5, served as a positive acting accessory factor for serum response factor (SRF) and together provided strong transcriptional activation of the cardiac alpha-actin promoter. In addition, Nkx-2.5 and SRF collaborated to activate the endogenous murine cardiac alpha-actin gene in 10T1/2 fibroblasts, by a mechanism that involved coassociation of SRF and Nkx-2.5 on intact SREs of the alpha-actin promoter. Here, we show that the second SRE of the avian cardiac alpha-actin promoter served as a binding site for Nkx-2.5, SRF, and zinc finger containing GLI-Kruppel-like factor, YY1. Expression of YY1 inhibited cardiac alpha-actin promoter activity, whereas coexpression of Nkx-2.5 and SRF was able to partially reverse YY1 repression. Displa...Continue Reading

Citations

Feb 18, 2004·Molecular and Cellular Biology·Charis L HimedaStephen D Hauschka
Jul 10, 2010·Circulation Research·Jun Wang, Robert J Schwartz
Aug 18, 2012·Journal of Cardiovascular Translational Research·Eric M Small

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