Early B Cell Factor 1 Regulates B Cell Gene Networks by Activation, Repression, and Transcription-Independent Poising of Chromatin
Early B Cell Factor 1 Regulates B Cell Gene Networks by Activation, Repression, and Transcription-Independent Poising of Chromatin
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DOI：
10.1016/j.immuni.2010.04.013
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发表时间：
2010-05-28
期刊：
影响因子：
32.4
通讯作者：
Grosschedl, Rudolf
中科院分区：
文献类型：
--
作者：
Treiber, Thomas;Mandel, Elizabeth M.;Grosschedl, Rudolf
转录因子早期B细胞因子-1 （Ebf1）是B谱系规范和分化的关键决定因素。为了深入了解Ebf1在早期B细胞中功能的分子基础，我们将全基因组ChIP测序分析与功能获得和功能丧失转录组分析相结合。在565个被Ebf1占据和转录调控的基因中，我们发现了大量涉及（前）b细胞受体和Akt信号传导、细胞粘附和迁移的基因。有趣的是，先前描述的Pax5靶标中有三分之一被Ebf1占据。除了Ebf1激活和抑制的基因外，我们还确定了Ebf1诱导染色质变化的靶标，这些变化在分化的后续阶段平衡了基因的表达。通过在T细胞中表达Ebf1而不是在NI H 3T3细胞中表达Ebf1，也可以在特定靶标上建立平衡的染色质状态，这表明Ebf1在造血染色质环境中充当“先锋”因子。
The transcription factor early B cell factor-1 (Ebf1) is a key determinant of B lineage specification and differentiation. To gain insight into the molecular basis of Ebf1 function in early-stage B cells, we combined a genome-wide ChIP sequencing analysis with gain- and loss-of-function transcriptome analyses. Among 565 genes that are occupied and transcriptionally regulated by Ebf1, we identified large sets involved in (pre)-B cell receptor and Akt signaling, cell adhesion, and migration. Interestingly, a third of previously described Pax5 targets was found to be occupied by Ebf1. In addition to Ebf1-activated and -repressed genes, we identified targets at which Ebf1 induces chromatin changes that poise the genes for expression at subsequent stages of differentiation. Poised chromatin states on specific targets could also be established by Ebf1 expression in T cells but not in NI H 3T3 cells, suggesting that Ebf1 acts as a "pioneer" factor in a hematopoietic chromatin context.