[HTML][HTML] The chromatin remodeler Mi-2β is required for CD4 expression and T cell development

CJ Williams, T Naito, P Gomez-del Arco, JR Seavitt… - Immunity, 2004 - cell.com
CJ Williams, T Naito, P Gomez-del Arco, JR Seavitt, SM Cashman, B De Souza, X Qi…
Immunity, 2004cell.com
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 …
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.
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