Integrated Department of Immunology, National Jewish Health, Denver, CO 80206, USA.
Curr Opin Immunol. 2010 Apr;22(2):177-84. doi: 10.1016/j.coi.2010.02.003. Epub 2010 Mar 6.
The generation of B lymphocytes from hematopoietic progenitors requires lineage-specific transcription factors that progressively direct cell fate choices. Differentiation of hematopoietic stem cells to lymphoid progenitors requires Ikaros-dependent lineage priming and graded levels of PU.1, which are controlled by Ikaros and Gfi1. E2A drives expression of EBF1, which initiates B lineage specification. EBF1, in addition to Pax5, is necessary for commitment to the B cell lineage. As a model of gene activation in early B lymphopoiesis, mb-1 genes are activated sequentially by factors (e.g. EBF1) that initiate chromatin modifications before transcription. This review highlights the requisite interplay between transcription factors and epigenetic mechanisms in the context of B cell development.
B 淋巴细胞由造血祖细胞生成,需要特异性转录因子来逐步指导细胞命运选择。造血干细胞向淋巴样祖细胞的分化需要依赖 Ikaros 的谱系启动和逐渐增加的 PU.1 水平,这由 Ikaros 和 Gfi1 控制。E2A 驱动 EBF1 的表达,从而启动 B 细胞谱系的特异性。EBF1 与 Pax5 一起,对于 B 细胞谱系的确定是必需的。作为早期 B 淋巴细胞发生中基因激活的模型,mb-1 基因被(如 EBF1)等因子依次激活,这些因子在转录前引发染色质修饰。本综述强调了转录因子和表观遗传机制在 B 细胞发育过程中的必要相互作用。