The regulatory network of B-cell differentiation: a focused view of early B-cell factor 1 function.
The regulatory network of B-cell differentiation: a focused view of early B-cell factor 1 function.
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DOI：
10.1111/imr.12206
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发表时间：
2014-09
影响因子：
8.7
通讯作者：
Grosschedl R
中科院分区：
文献类型：
--
作者：
Boller S;Grosschedl R
在过去的几十年里，许多研究已经研究了造血系统中谱系决定的转录和表观遗传调节。这些努力导致了一个模型，在该模型中，外部信号和内在信号建立了允许的染色质环境，在此基础上，转录因子和表观遗传修饰物的调控网络作用于指导造血谱系的分化。这些网络包括谱系特定的因子，这些因子进一步改变表观遗传格局，促进特定细胞类型的产生。B淋巴细胞的生成过程需要一系列转录因子，包括Ikaros、PU.1、E2a和FoxO1，这些转录因子被B系特异性转录因子EBF1和Pax-5激活。EBF1的表达是由E2A和FoxO1共同作用启动的，包括Pax-5和IL-7信号在内的几个正反馈环进一步增强和维持EBF1的表达。EBF1与Ikaros、PU.1、RUNX1、E2a、FoxO1和Pax-5协同作用，建立B细胞特异性转录图谱。EBF1和Pax-5还合作抑制可供选择的细胞命运，并将细胞锁定在B系命运中。除了EBF1在建立和维持B细胞特性方面的功能外，EBF1还需要协调分化与细胞增殖和生存。
During the last decades, many studies have investigated the transcriptional and epigenetic regulation of lineage decision in the hematopoietic system. These efforts led to a model in which extrinsic signals and intrinsic cues establish a permissive chromatin context upon which a regulatory network of transcription factors and epigenetic modifiers act to guide the differentiation of hematopoietic lineages. These networks include lineage-specific factors that further modify the epigenetic landscape and promote the generation of specific cell types. The process of B lymphopoiesis requires a set of transcription factors, including Ikaros, PU.1, E2A, and FoxO1 to ‘prime’ cis-regulatory regions for subsequent activation by the B-lineage-specific transcription factors EBF1 and Pax-5. The expression of EBF1 is initiated by the combined action of E2A and FoxO1, and it is further enhanced and maintained by several positive feedback loops that include Pax-5 and IL-7 signaling. EBF1 acts in concert with Ikaros, PU.1, Runx1, E2A, FoxO1, and Pax-5 to establish the B cell-specific transcription profile. EBF1 and Pax-5 also collaborate to repress alternative cell fates and lock cells into the B-lineage fate. In addition to the functions of EBF1 in establishing and maintaining B-cell identity, EBF1 is required to coordinate differentiation with cell proliferation and survival.
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影响因子：
30.5
作者：
通讯作者：
--
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影响因子：
32.4
作者：
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通讯作者：
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15.3
作者：
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通讯作者：
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15.3
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通讯作者：
Murre, Cornelis
影响因子：
20.3
作者：
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通讯作者：
Merkenschlager, Matthias