MTA3 and the Mi-2/NuRD complex regulate cell fate during B lymphocyte differentiation
MTA3 and the Mi-2/NuRD complex regulate cell fate during B lymphocyte differentiation
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DOI：
10.1016/j.cell.2004.09.014
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发表时间：
2004-10-01
期刊：
影响因子：
64.5
通讯作者：
Wade, PA
中科院分区：
文献类型：
--
作者：
Fujita, N;Jaye, DL;Wade, PA
在生发中心反应中，转录抑制因子BCL-6通过阻止B淋巴细胞最终分化为浆细胞来调节B淋巴细胞的命运，直到收到适当的信号。在这里，我们报告了一个辅助因子MTA3，一个辅助抑制因子复合物Mi-2/ NuRD的细胞类型特异性亚基，用于bcl -6依赖性细胞命运的决定。MTA3在生发中心的表达模式与BCL-6相同。BCL-6与Mi-2/NuRD相互作用，这种相互作用对BCL-6乙酰化状态敏感。RNAi对MTA3的损耗会损害bcl -6依赖性抑制，并改变B淋巴细胞细胞特异性转录模式的特征。值得注意的是，BCL-6在浆细胞系中的外源表达，以mta3依赖的方式，导致浆细胞特异性转录物的抑制，B细胞转录程序的再激活，B淋巴细胞细胞表面标记物的表达，以及细胞命运的重编程。
The transcriptional repressor BCL-6 regulates B lymphocyte cell fate during the germinal center reaction by preventing terminal differentiation of B lymphocytes into plasma cells until appropriate signals are received. Here, we report a cofactor, MTA3, a cell type-specific subunit of the corepressor complex Mi-2/ NuRD, for BCL-6-dependent cell fate determination. MTA3 is expressed in the same pattern in germinal centers as BCL-6. BCL-6 physically interacts with Mi-2/NuRD and this interaction is sensitive to BCL-6 acetylation status. Depletion of MTA3 by RNAi impairs BCL-6-dependent repression and alters the cell-specific transcriptional pattern characteristic of the B lymphocyte. Remarkably, exogenous expression of BCL-6 in a plasma cell line leads, in an MTA3-dependent manner, to repression of plasma cell-specific transcripts, reactivation of the B cell transcriptional program, expression of B lymphocyte cell surface markers, and reprogramming of cell fate.