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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


  • Williams CJ
  • Naito T
  • Arco PG
  • Seavitt JR
  • Cashman SM
  • De Souza B
  • Qi X
  • Keables P
  • Von Andrian UH
  • Georgopoulos K



Publication Data

June 10, 2004

Associated Grants

  • Agency: NIAID NIH HHS, Id: R01-AI1380342-09

Mesh Terms

  • 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