The chromatin remodeler Brg1 activates enhancer repertoires to establish B cell identity and modulate cell growth.

The chromatin remodeler Brg1 activates enhancer repertoires to establish B cell identity and modulate cell growth.
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DOI:
10.1038/ni.3170
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发表时间:
2015-07
期刊:
影响因子:
30.5
通讯作者:
--
中科院分区:
医学1区
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--
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早期B细胞发育是由转录调节因子E2 A、EBF 1、Foxo 1和Ikaros的组合活性协调的。然而,如何在B系发育过程中调节这些调节因子的全基因组结合模式仍有待确定。在这里,我们发现,在淋巴祖细胞的染色质重塑Brg 1指定的B细胞的命运。在定向前B细胞中,Brg1调节Igh位点收缩并控制Myc表达,以调节调节核糖体生物合成的基因的表达。在承诺前B细胞Brg1抑制前B谱系特异性模式的基因表达。最后,我们发现Brg 1通过促进谱系特异性转录因子进入平衡的增强子库来建立B细胞命运和调节细胞生长。
Early B cell development is orchestrated by the combined activities of the transcriptional regulators E2A, EBF1, Foxo1 and Ikaros. However, how the genome-wide binding patterns of these regulators are modulated during B-lineage development remains to be determined. Here, we found that in lymphoid progenitors the chromatin remodeler Brg1 specified the B cell fate. In committed pro-B cells Brg1 regulated Igh locus contraction and controlled Myc expression to modulate the expression of genes that regulate ribosome biogenesis. In committed pro-B cells Brg1 suppressed a pre-B lineage-specific pattern of gene expression. Finally, we found that Brg1 acted mechanistically to establish B cell fate and modulate cell growth by facilitating access of lineage-specific transcription factors to poised enhancer repertoires.
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