The chromatin remodeler Mi-2beta is required for CD4 expression and T cell development.
Changes in chromatin structure underlie the activation or silencing of genes during development. The chromatin remodeler Mi-2beta is highly expressed in thymocytes and is presumed to be a transcriptional repressor because of its presence in the nucleosome remodeling deacetylase (NuRD) complex. Using conditional inactivation, we show that Mi-2beta is required at several steps during T cell development: for differentiation of beta selected immature thymocytes, for developmental expression of CD4, and for cell divisions in mature T cells. We further show that Mi-2beta plays a direct role in promoting CD4 gene expression. Mi-2beta associates with the CD4 enhancer as well as the E box binding protein HEB and the histone acetyltransferase (HAT) p300, enabling their recruitment to the CD4 enhancer and causing histone H3-hyperacetylation to this regulatory region. These findings provide important insights into the regulation of CD4 expression during T cell development and define a role for Mi-2beta in gene activation.
Pubmed ID: 15189737 RIS Download
Acetyltransferases | Animals | Antigens, CD4 | Apoptosis | Basic Helix-Loop-Helix Transcription Factors | Cell Cycle Proteins | Cell Differentiation | Cell Division | Cells, Cultured | Chromatin Assembly and Disassembly | DNA-Binding Proteins | Enhancer Elements, Genetic | Flow Cytometry | Gene Expression Regulation | Histone Acetyltransferases | Histone Deacetylases | Mi-2 Nucleosome Remodeling and Deacetylase Complex | Mice | Mice, Transgenic | Receptors, Antigen, T-Cell | T-Lymphocytes | Thymus Gland | Transcription Factors | Transcriptional Activation | Transgenes | p300-CBP Transcription Factors