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Originally published In Press as doi:10.1074/jbc.M201821200 on April 9, 2002

J. Biol. Chem., Vol. 277, Issue 27, 24081-24089, July 5, 2002
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CREB-binding Protein/p300 Co-activation of Crystallin Gene Expression*

Qin Chen, Dennis H. Dowhan, Dongcai Liang, David D. Moore, and Paul A. OverbeekDagger

From the Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030

Although some of the transcription factors that are required for expression of crystallins during lens development have been identified, the molecular interactions that contribute to enhanced crystallin expression are not yet well defined. In this study, we designed experiments to test whether the co-activators CREB-binding protein (CBP) and/or p300 interact with c-Maf, Prox-1, or Sox-1 to enhance transcription of crystallin genes. Promoter regions from the mouse alpha A-, beta B2-, and gamma F-crystallin genes were linked to a luciferase reporter. Expression of c-Maf transactivated each of these promoters. Of particular interest, co-expression of CBP or p300 with c-Maf was found to synergistically co-activate each promoter. CBP and p300 were less effective or ineffective at co-activation with Prox-1 or Sox-1. Co-immunoprecipitation and mammalian two-hybrid experiments revealed that CBP and p300 bind to c-Maf and Prox-1 but not to Sox-1. The co-activation of c-Maf by CBP/p300 requires histone acetyltransferase activity. Our results suggest that c-Maf recruits CBP and/or p300 to crystallin promoters leading to up-regulation of crystallin gene expression through localized histone acetylation and consequent chromatin re-modeling. In a promoter-specific fashion, co-activation can be modulated by Prox-1 and/or Sox-1. This modulation may help to specify the endogenous levels of crystallin gene expression.

* This work was supported by National Institutes of Health Grants EY10448, EY10803, and EY11348 (to P. A. O.) and a grant from the Knights Templar Eye Foundation (to Q. C.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: Dept. of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Tel.: 713-798-6421; Fax: 713-790-1275; E-mail: overbeek@bcm.tmc.edu.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.


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