2012年11月21日 讯 /生物谷BIOON/ --血细胞发育过程称为造血，使人产生许多不同的免疫细胞亚型。现有研究认为三种转录因子E2A，EBF1和PAX5促使功能性B淋巴细胞成熟。近日，Wooseok等研究人员证实E2A是EBF1表达的所必需的。Seo和Taniuchi研究了另一种转录因子Runx1，Runx1是血细胞发育的一个重要组成部分。没有Runx1，造血是不可能发生的。
研究人员利用除了早期B细胞前体，每一个细胞都表达Runx1的转基因工程小鼠来探究Runx1在B细胞发育中的作用。结果发现没有Runx1，这些细胞停滞在发育的早期。
Seo和他的同事们证实Runx1联合Cbfβ蛋白，通常结合调节EBF1生成的启动子序列上。有趣的是，EBF1有两种截然不同的启动子，RUNX1-Cbfβ和E2A每个绑定到EBF1不同的启动子上。
在Runx1存在情况下，EBF1基因活性大幅降低，能阻断EBF1下游诱导的B细胞分化的最后一步。然而，Runx1能开启编码其上游激活因子E2A的基因，激活正反馈环路，从而加速B细胞分化过程，因此，如果没有Runx1，三个分化因素就不会正确表达。
目前，研究人员正在探索Runx1控制基因活性的机制，以及是如何能够发挥这样一个强有力的促造血发育功能的。（生物谷：Bioon.com）
doi:10.1084/jem.20112745
PMC:
PMID:
Runx1–Cbfβ facilitates early B lymphocyte development by regulating expression of Ebf1.
Seo, W., Ikawa, T., Kawamoto, H. & Taniuchi, I.
Although Runx and Cbfβ transcription factor complexes are involved in the development of multiple hematopoietic lineages, their precise roles in early mouse B lymphocyte differentiation remain elusive. In this study, we examined mouse strains in which Runx1, Runx3, or Cbfβ were deleted in early B lineage progenitors by an mb1-cre transgene. Loss of Runx1, but not Runx3, caused a developmental block during early B lymphopoiesis, resulting in the lack of IgM+ B cells and reduced VH to DJH recombination. Expression of core transcription factors regulating early B cell development, such as E2A, Ebf1, and Pax5, was reduced in B cell precursors lacking Runx1. We detected binding of Runx1–Cbfβ complexes to the Ebf1 proximal promoter, and these Runx-binding motifs were essential to drive reporter gene expression. Runx1-deficient pro-B cells harbored excessive amounts of the repressive histone mark H3K27 trimethylation in the Ebf1 proximal promoter. Interestingly, retroviral transduction of Ebf1, but not Pax5, into Runx1-deficient progenitors restored not only development of B220+ cells that underwent VH to DJH rearrangement but also expression of B lineage signature genes. Collectively, these results demonstrate that Runx1–Cbfβ complexes are essential to facilitate B lineage specification, in part via epigenetic activation of the Ebf1 gene.
