Regulation of the calreticulin gene by GATA6 and Evi-1 transcription factors.
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.
Qiu
Yuanyuan
Y
Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2H7.
Lynch
Jeffrey
J
Guo
Lei
L
Yatsula
Bogdan
B
Perkins
Archibald S
AS
Michalak
Marek
M
D000818:Animals; D037282:Calreticulin / Q000235:genetics*; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000502:physiology*; D024202:Electrophoretic Mobility Shift Assay; D050993:GATA6 Transcription Factor / Q000502:physiology*; D000074008:MDS1 and EVI1 Complex Locus Protein; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D041681:NIH 3T3 Cells; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000502:physiology; D011519:Proto-Oncogenes / Q000502:physiology*; D051381:Rats; D014157:Transcription Factors / Q000502:physiology*
D037282:Calreticulin; D004268:DNA-Binding Proteins; D050993:GATA6 Transcription Factor; D000074008:MDS1 and EVI1 Complex Locus Protein; C499305:Mecom protein, mouse; D014157:Transcription Factors