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Interacts with Histone Deacetylase 1 to Repress Promoter Activity1
,
* Department of Pediatrics, Division of Rheumatology, University Hospital, University of Muenster, Muenster, Germany;
Institute of Experimental Dermatology, University of Muenster, Muenster, Germany;
Interdisciplinary Center for Clinical Research, Research Group 5, University of Muenster, Muenster, Germany; and
Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910
Transcriptional repression is a fundamental mechanism of gene regulation. cAMP response element (CRE) modulator (CREM)
is an ubiquitously expressed transcription factor and a counterpart of the activator CREB. In T cells, CREM is responsible for the termination of the IL-2 expression by a chromatin-dependent mechanism. We demonstrate in this study that CREM associates with histone deacetylase (HDAC)1 through its H domain, which is located between the kinase inducible and DNA binding domains. The CREM-mediated recruitment of HDAC1 to the CRE sites of the IL-2 and c-Fos promoter causes histone deacetylation and inaccessibility to restriction enzymes and limited transcriptional activity. Importantly, the CRE sites of these promoters are crucial for the activity and binding of HDAC1. Therefore, CREM exerts its repressor activity by a mechanism that involves recruitment of HDAC1, increased deacetylation of histones, and repression of promoter activity.
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 The work was supported by the Interdisciplinary Center for Clinical Research (Interdisziplinäres Zentrum für Klinische Forschung), Research Group 5, and Public Health Service Grant RO1 AI49954 (to G.C.T.).
2 Address correspondence and reprint requests to Dr. Klaus Tenbrock, University of Muenster, Experimental Dermatology, Röntgenstrasse 21, 48149 Muenster, Germany. E-mail address: ktenbroc{at}uni-muenster.de
3 Abbreviations used in this paper: CRE, cAMP response element; CREM, CRE modulator; SLE, systemic lupus erythematosus; HDAC, histone deacetylase; ChIP, chromatin immunoprecipitation; KID, kinase inducible domain; DBD, DNA binding domain; R-ChIP, reporter-based ChIP; HAT, histone acetyltransferase; SAHA, superoylanilide hydroxamic acid; NP-40, Nonidet P-40.
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