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转录抑制因子 Bach2 和 Bach1 通过抑制髓系程序促进 B 细胞发育。

The transcription repressors Bach2 and Bach1 promote B cell development by repressing the myeloid program.

机构信息

1] Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan. [2] CREST, Japan Science and Technology Agency, Sendai, Japan.

Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.

出版信息

Nat Immunol. 2014 Dec;15(12):1171-80. doi: 10.1038/ni.3024. Epub 2014 Oct 26.

DOI:10.1038/ni.3024
PMID:25344725
Abstract

Mature lymphoid cells express the transcription repressor Bach2, which imposes regulation on humoral and cellular immunity. Here we found critical roles for Bach2 in the development of cells of the B lineage, commencing from the common lymphoid progenitor (CLP) stage, with Bach1 as an auxiliary. Overexpression of Bach2 in pre-pro-B cells deficient in the transcription factor EBF1 and single-cell analysis of CLPs revealed that Bach2 and Bach1 repressed the expression of genes important for myeloid cells ('myeloid genes'). Bach2 and Bach1 bound to presumptive regulatory regions of the myeloid genes. Bach2(hi) CLPs showed resistance to myeloid differentiation even when cultured under myeloid conditions. Our results suggest that Bach2 functions with Bach1 and EBF1 to promote B cell development by repressing myeloid genes in CLPs.

摘要

成熟的淋巴细胞表达转录抑制因子 Bach2,它对体液和细胞免疫施加调节作用。在这里,我们发现 Bach2 在 B 细胞谱系细胞的发育中起着关键作用,从共同淋巴祖细胞(CLP)阶段开始,Bach1 作为辅助因子。在转录因子 EBF1 缺失的前 B 细胞中过表达 Bach2 ,以及对 CLP 的单细胞分析表明,Bach2 和 Bach1 抑制了对髓系细胞(“髓系基因”)重要的基因的表达。Bach2 和 Bach1 结合到髓系基因的假定调节区域。Bach2(hi) CLP 即使在髓系条件下培养也表现出对髓系分化的抗性。我们的结果表明,Bach2 与 Bach1 和 EBF1 一起通过抑制 CLP 中的髓系基因来促进 B 细胞发育。

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