The Chromatin Remodeler Mi-2[beta] Is Required for CD4 Expression and T Cell Development

• Published in: Immunity (Cambridge, Mass.) Mass.), 2004-06, Vol.20 (6), p.719
• Main Authors: Williams, Christine J, Naito, Taku, Arco, Pablo Gómez-del, Seavitt, John R, Cashman, Susan M, De Souza, Beverly, Qi, Xiaoqing, Keables, Piper, Von Andrian, Ulrich H, Georgopoulos, Katia
• Format: Article
• Language: English
• Subjects: Chromatin; Deoxyribonucleic acid; DNA; Gene expression; Lymphocytes; Peptides; Proteins; Scholarships & fellowships; T cell receptors
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2004.05.005

Changes in chromatin structure underlie the activation or silencing of genes during development. The chromatin remodeler Mi-2β 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-2β is required at several steps during T cell development: for differentiation of β selected immature thymocytes, for developmental expression of CD4, and for cell divisions in mature T cells. We further show that Mi-2β plays a direct role in promotingCD4gene expression. Mi-2β associates with theCD4enhancer as well as the E box binding protein HEB and the histone acetyltransferase (HAT) p300, enabling their recruitment to theCD4enhancer and causing histone H3-hyperacetylation to this regulatory region. These findings provide important insights into the regulation ofCD4expression during T cell development and define a role for Mi-2β in gene activation.