The SWI/SNF-like BAF Complex Is Essential for Early B Cell Development

The SWI/SNF-like BAF Complex Is Essential for Early B Cell Development
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DOI:
10.4049/jimmunol.1103390
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发表时间:
2012-04-15
影响因子:
4.4
通讯作者:
Seong, Rho H.
Seong, Rho H.
中科院分区:
医学2区
文献类型:
--
作者:
Choi, Jinwook;Ko, Myunggon;Seong, Rho H.

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在B细胞发育过程中,转录因子如E2 A和Ebf 1已被认为起着关键作用。尽管转录因子和染色质调节因子协同作用指导B谱系特异性基因的表达,但对B淋巴细胞生成过程中染色质结构调节因子的参与知之甚少。在这篇文章中,我们表明,Srg 3/mBaf 155,支架亚基的SWI/SNF样BAF复合物,在造血细胞系中的缺失造成的缺陷,在共同的淋巴祖细胞阶段和过渡从前亲B早期亲B细胞由于失败的表达B谱系特异性基因,如Ebf 1和Il 7 ra,和他们的下游靶基因。此外,缺乏Brg 1(具有ATP酶活性的复合物的亚基)表达的小鼠也表现出早期B细胞发育的缺陷。我们还发现Ebf 1和Il 7 ra的表达受SWI/SNF-like BAF复合物的直接调控。因此,我们的研究结果表明,SWI/SNF样BAF复合物通过调节B谱系特异性基因的表达促进早期B细胞发育。免疫学杂志,2012,188:3791-3803。
During the process of B cell development, transcription factors, such as E2A and Ebf1, have been known to play key roles. Although transcription factors and chromatin regulators work in concert to direct the expression of B lineage-specific genes, little is known about the involvement of regulators for chromatin structure during B lymphopoiesis. In this article, we show that deletion of Srg3/mBaf155, a scaffold subunit of the SWI/SNF-like BAF complex, in the hematopoietic lineage caused defects at both the common lymphoid progenitor stage and the transition from pre-pro-B to early pro-B cells due to failures in the expression of B lineage-specific genes, such as Ebf1 and Il7ra, and their downstream target genes. Moreover, mice that were deficient in the expression of Brg1, a subunit of the complex with ATPase activity, also showed defects in early B cell development. We also found that the expression of Ebf1 and Il7ra is directly regulated by the SWI/SNF-like BAF complex. Thus, our results suggest that the SWI/SNF-like BAF complex facilitates early B cell development by regulating the expression of B lineage-specific genes. The Journal of Immunology, 2012, 188: 3791-3803.