COUP-TF1 antagonizes Nkx2.5-mediated activation of the calreticulin gene during cardiac development.
Calreticulin, a Ca(2+) binding chaperone of the endoplasmic reticulum, is also highly expressed in the embryonic heart, and knockout of the calreticulin gene is lethal during embryogenesis because of impaired cardiac development. The protein is down-regulated after birth, and elevated expression of calreticulin in newborn hearts is associated with severe cardiac pathology and death. Here we show that the transcription factor Nkx2.5 activates expression of the calreticulin gene in the heart. Binding of chicken ovalbumin upstream promoter-transcription factor 1 to the Nkx2.5 binding site suppresses transcription from the calreticulin promoter. Nkx2.5 and chicken ovalbumin upstream promoter-transcription factor 1 play antagonistic roles in regulating the expression of calreticulin during cardiac development. These studies indicate that cardiac-specific transcription factor Nkx2.5 plays a central role in activating calreticulin expression and that there is a cooperation between chicken ovalbumin upstream promoter-transcription factor 1 and Nkx2.5 at the calreticulin promoter.
Guo
L
L
Canadian Institutes of Health Research Group in Molecular Biology of Membrane Proteins, University of Alberta, Edmonton, Alberta, Canada.
Lynch
J
J
Nakamura
K
K
Fliegel
L
L
Kasahara
H
H
Izumo
S
S
Komuro
I
I
Agellon
L B
LB
Michalak
M
M
D000818:Animals; D001665:Binding Sites; D051838:COUP Transcription Factor I; D002135:Calcium-Binding Proteins / Q000235:genetics*; D037282:Calreticulin; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000378:metabolism*; D051379:Mice; D008957:Models, Genetic; D018832:Molecular Chaperones / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020218:Response Elements; D012261:Ribonucleoproteins / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D029867:Xenopus Proteins
D051838:COUP Transcription Factor I; D002135:Calcium-Binding Proteins; D037282:Calreticulin; D004268:DNA-Binding Proteins; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; D018832:Molecular Chaperones; C095552:NKX2-5 protein, human; C484469:Nkx2-5 protein, mouse; C497590:Nr2f1 protein, mouse; D012261:Ribonucleoproteins; D014157:Transcription Factors; D029867:Xenopus Proteins