The B-cell identity factor Pax5 regulates distinct transcriptional programmes in early and late B lymphopoiesis
The B-cell identity factor Pax5 regulates distinct transcriptional programmes in early and late B lymphopoiesis
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DOI：
10.1038/emboj.2012.155
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发表时间：
2012-07-18
期刊：
影响因子：
11.4
通讯作者：
Busslinger, Meinrad
中科院分区：
文献类型：
--
作者：
Revilla-i-Domingo, Roger;Bilic, Ivan;Busslinger, Meinrad
Pax5通过抑制谱系不合适基因和激活B细胞特异性基因来控制B细胞的身份和发育。在这里，我们使用全基因组方法鉴定了前B细胞和成熟B细胞中的Pax5靶基因。在这些细胞类型中，Pax5与40%的顺式调控元件结合，这些顺式调控元件是通过定位dna酶I超敏（DHS）位点、转录起始位点和组蛋白修饰来定义的。虽然Pax5能结合8000个靶基因，但在前B细胞和成熟B细胞中，它通过在活化基因处诱导增强子和消除抑制基因处的DHS位点来调节其中的4%。在前b细胞中，Pax5调控的基因占了发生在普通淋巴样祖细胞和承诺的前b细胞之间的所有表达变化的23%，这表明Pax5是这一发育转变的重要调节因子。受调控的Pax5靶基因在前B细胞和成熟B细胞中重叠最小，这反映了这些细胞类型之间的大量表达变化。因此，Pax5通过调节早期和晚期B淋巴生成中不同的靶基因来控制B细胞的身份和功能。中国生物医学工程学报（2012），31(3),3130-3146。doi: 10.1038 / emboj.2012.155;2012年6月5日在线发布
Pax5 controls the identity and development of B cells by repressing lineage-inappropriate genes and activating B-cell-specific genes. Here, we used genome-wide approaches to identify Pax5 target genes in pro-B and mature B cells. In these cell types, Pax5 bound to 40% of the cis-regulatory elements defined by mapping DNase I hypersensitive (DHS) sites, transcription start sites and histone modifications. Although Pax5 bound to 8000 target genes, it regulated only 4% of them in pro-B and mature B cells by inducing enhancers at activated genes and eliminating DHS sites at repressed genes. Pax5-regulated genes in pro-B cells account for 23% of all expression changes occurring between common lymphoid progenitors and committed pro-B cells, which identifies Pax5 as an important regulator of this developmental transition. Regulated Pax5 target genes minimally overlap in pro-B and mature B cells, which reflects massive expression changes between these cell types. Hence, Pax5 controls B-cell identity and function by regulating distinct target genes in early and late B lymphopoiesis. The EMBO Journal (2012) 31, 3130-3146. doi:10.1038/emboj.2012.155; Published online 5 June 2012