The Chromatin Remodeler Mi-2β Is Required for CD4 Expression and T Cell Development

Abstract

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 promoting CD4 gene expression. Mi-2β 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-2β in gene activation.