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Activating Transcription Factor/cAMP Response Element Binding Protein Family Member Regulated Transcription of CD1A¹

Department of Pathology, University of Chicago, Chicago, IL 60637

CD1a has a unique expression pattern among Ag-presenting molecules, expressed specifically on cortical thymocytes and APCs. As autoimmune disease, infection, and tumors can all result in alteration of CD1a expression, we are attempting to characterize the transcriptional regulation, and thus shed some light on specific expression, of CD1A. In this study, we have identified a minimal proximal promoter region required for CD1A transcription. Computer searches within this region identified numerous potential binding sites for lymphoid-specific transcription factors, including the ETS transcription factors, C/EBP, GATA, and CREB. Deletion and site-specific mutant analysis revealed a critical role of a potential cAMP response element (CRE) 965 bp upstream of the CD1A translation start site. Two activating transcription factor (ATF)/CREB family members, CREB-1 and ATF-2, are able to bind this site in vitro and in vivo. Notably, activation of ATF/CREB family members decreases CD1A transcription, while decrease in ATF-2 expression results in increased CD1A RNA level. The fact that these factors also bind the CD1A promoter in human monocytes strongly suggests a role for ATF/CREB family members in regulation of CD1A expression.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grant AI057460 (to C.-R.W.).

² Address correspondence and reprint requests to Dr. Chyung-Ru Wang, Department of Pathology, University of Chicago, 924 East 57th Street, Biological Sciences Learning Center R116, Chicago, IL 60637-5420. E-mail address: cwang{at}uchicago.edu

³ Abbreviations used in this paper: CRE, cAMP response element; ATF, activating transcription factor; h, human; ChIP, chromatin immunoprecipitation; CREM, cAMP responsive element modulator; shRNA, short hairpin RNA; DNCREB, dominant-negative CREB.

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