The transcriptional repressor cAMP response element modulator alpha interacts with histone deacetylase 1 to repress promoter activity.
Transcriptional repression is a fundamental mechanism of gene regulation. cAMP response element (CRE) modulator (CREM)alpha 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 CREMalpha associates with histone deacetylase (HDAC)1 through its H domain, which is located between the kinase inducible and DNA binding domains. The CREMalpha-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, CREMalpha exerts its repressor activity by a mechanism that involves recruitment of HDAC1, increased deacetylation of histones, and repression of promoter activity.
Tenbrock
Klaus
K
Department of Pediatrics, Division of Rheumatology, University Hospital, University of Muenster, Röntgenstrasse 21, 48149 Muenster, Germany. ktenbroc@uni-muenster.de
Juang
Yuang-Taung
YT
Leukert
Nadja
N
Roth
Johannes
J
Tsokos
George C
GC
D000107:Acetylation; D001665:Binding Sites; D002478:Cells, Cultured; D051786:Cyclic AMP Response Element Modulator / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005786:Gene Expression Regulation; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D017434:Protein Structure, Tertiary; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D012097:Repressor Proteins / Q000378:metabolism*
D006657:Histones; D007376:Interleukin-2; D016760:Proto-Oncogene Proteins c-fos; D012097:Repressor Proteins; D051786:Cyclic AMP Response Element Modulator; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases