The chromatin remodeler Mi-2beta is required for CD4 expression and T cell development.
Journal:
Immunity 2004 JunAuthors:
Williams CJ, Naito T, Arco PG, Seavitt JR, Cashman SM, De Souza B, Qi X, Keables P, Von Andrian UH, Georgopoulos K
Abstract
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,
...[more]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.[less]
Mesh Headings:
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