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. 2008 Mar 25;47(12):3697-704.
doi: 10.1021/bi702524v. Epub 2008 Feb 28.

Regulation of the calreticulin gene by GATA6 and Evi-1 transcription factors

Yuanyuan Qiu  1 , Jeffrey Lynch, Lei Guo, Bogdan Yatsula, Archibald S Perkins, Marek Michalak
Affiliations

Regulation of the calreticulin gene by GATA6 and Evi-1 transcription factors

Yuanyuan Qiu et al. Biochemistry. .

Abstract

Calreticulin is a Ca (2+)-buffering chaperone of the endoplasmic reticulum. The protein is highly expressed in embryonic heart but downregulated in postnatal heart, indicating that expression of calreticulin in the heart is highly regulated. In this study we identify GATA6 and Evi-1 transcription factors as new regulators of the calreticulin gene. In neonatal rat ventricular cardiomyocytes and mouse fibroblasts the calreticulin gene is activated by GATA6 but repressed by Evi-1. Furthermore, transactivation of the calreticulin gene by GATA6 is suppressed by Evi-1, suggesting an antagonistic role between both GATA6 and Evi-1. Using EMSA, ChIP analysis, and site-specific mutagenesis, we showed that GATA6 and Evi-1 bind to site 1 on the calreticulin promoter. GATA6 and Evi-1 are highly expressed early during cardiogenesis of ES cells, suggesting that they may regulate expression of the calreticulin gene during cardiac development.

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