Department of Molecular Biology, University of California, San Diego, La Jolla, California, USA.
Nat Immunol. 2010 Jul;11(7):635-43. doi: 10.1038/ni.1891. Epub 2010 Jun 13.
It is now established that the transcription factors E2A, EBF1 and Foxo1 have critical roles in B cell development. Here we show that E2A and EBF1 bound regulatory elements present in the Foxo1 locus. E2A and EBF1, as well as E2A and Foxo1, in turn, were wired together by a vast spectrum of cis-regulatory sequences. These associations were dynamic during developmental progression. Occupancy by the E2A isoform E47 directly resulted in greater abundance, as well as a pattern of monomethylation of histone H3 at lysine 4 (H3K4) across putative enhancer regions. Finally, we divided the pro-B cell epigenome into clusters of loci with occupancy by E2A, EBF and Foxo1. From this analysis we constructed a global network consisting of transcriptional regulators, signaling and survival factors that we propose orchestrates B cell fate.
现在已经确定转录因子 E2A、EBF1 和 Foxo1 在 B 细胞发育中具有关键作用。在这里，我们表明 E2A 和 EBF1 结合了 Foxo1 基因座中存在的调节元件。E2A 和 EBF1 以及 E2A 和 Foxo1 反过来又通过大量的顺式调节序列连接在一起。这些关联在发育过程中是动态的。E2A 同工型 E47 的占据直接导致了更多的丰度，以及在假定的增强子区域中组蛋白 H3 赖氨酸 4（H3K4）的单甲基化模式。最后，我们将前 B 细胞表观基因组划分为 E2A、EBF 和 Foxo1 占据的基因座簇。通过这项分析，我们构建了一个由转录调节剂、信号和存活因子组成的全局网络，我们提出该网络协调 B 细胞命运。
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