The transcriptional repressor cAMP response element modulator α interacts with histone deacetylase 1 to repress promoter activity

Transcriptional repression is a fundamental mechanism of gene regulation. cAMP response element (CRE) modulator (CREM)a 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 alpha associates with histone deacetylase (HDAC)1 through its H domain, which is located between the kinase inducible and DNA binding domains. The CREM alpha-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, CREMa exerts its repressor activity by a mechanism that involves recruitment of HDAC1, increased deacetylation of histories, and repression of promoter activity.