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Papers In Press, published online ahead of print April 9, 2002
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030
Corresponding Author: overbeek{at}bcm.tmc.edu
Multiple transcription factors are required for expression of crystallins during lens development. How they interact with coactivators in regulation of expression of crystallin genes is not yet known. In this study, We designed experiments to test whether coactivators CBP and/or p300 interact with c-maf, Prox-1, Sox-1 and Pax-6 to activate transcription of crystallin genes. We also assayed for cooperative or antagonistic interactions between the different transcription factors. Promoter regions from the mouse alphaA-, betaB2- and gammaF-crystallin genes were linked to a luciferase reporter, and transfected into Cos-1 cells. All three crystallin promoters were transactivated by c-maf alone. Only the gammaF-crystallin reporter was activated by Sox-1. CBP or p300 coactivated c-maf, but not Sox-1, mediated promoter transactivation. In general, coactivation was enhanced by Prox-1, but repressed by Sox-1. Coimmunoprecipitation and mammalian two hybrid experiments revealed that CBP and p300 bind to c-maf and Prox-1 but not Sox-1. The coactivation by CBP/p300 requires histone acetyltransferae (HAT) activity. Stimulation by CBP/p300 can be duplicated by expression of a c-maf-HAT fusion protein. Our results suggest that crystallin gene expression can be induced by a c-maf/CBP/p300 complex through histone acetylation. Coactivation can be enhanced by Prox-1 and inhibited by Sox-1 to maintain a balance of crystallin gene expression.
J. Biol. Chem, 10.1074/jbc.M201821200
Submitted on February 22, 2002
Revised on March 27, 2002
Accepted on April 9, 2002
CBP/p300 coactivation of crystallin gene expression
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