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
Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
Immunity. 2004 Jun;20(6):719-33. 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-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.
染色质结构的变化是发育过程中基因激活或沉默的基础。染色质重塑因子Mi-2β在胸腺细胞中高度表达，由于其存在于核小体重塑去乙酰化酶（NuRD）复合物中，被认为是一种转录抑制因子。通过条件性失活，我们发现Mi-2β在T细胞发育的几个步骤中是必需的：对于β选择的未成熟胸腺细胞的分化、CD4的发育性表达以及成熟T细胞中的细胞分裂。我们进一步表明，Mi-2β在促进CD4基因表达中起直接作用。Mi-2β与CD4增强子以及E盒结合蛋白HEB和组蛋白乙酰转移酶（HAT）p300相关联，使其能够募集到CD4增强子并导致该调控区域的组蛋白H3超乙酰化。这些发现为T细胞发育过程中CD4表达的调控提供了重要见解，并确定了Mi-2β在基因激活中的作用。
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