Proximity among Distant Regulatory Elements at the β-Globin Locus Requires GATA-1 and FOG-1
Proximity among Distant Regulatory Elements at the β-Globin Locus Requires GATA-1 and FOG-1
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DOI：
10.1016/j.molcel.2004.12.028
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发表时间：
2005-02-04
期刊：
影响因子：
16
通讯作者：
Blobel, GA
中科院分区：
文献类型：
--
作者：
Vakoc, CR;Letting, DL;Blobel, GA
最近的证据表明，远程增强子和基因启动子非常接近，这可能反映了染色质环的形成。在这里，我们研究了DNA环在-珠蛋白位点的机制。通过染色体构象捕获（3C），我们发现造血转录因子GATA-1及其辅因子fg -1是β -珠蛋白基因座控制区（LCR）和β -主珠蛋白启动子之间物理相互作用所必需的。动力学研究表明，gata -1诱导的环形成与β -珠蛋白转录的开始相关，并且独立于新蛋白的合成。在缺乏LCR的小鼠的胎肝红母细胞中，GATA-1通常占据β -主珠蛋白启动子，这表明GATA-1与启动子和LCR的结合是发生在环形成之前的独立事件。总之，这些数据表明GATA-1和fog1是组织特异性染色质环的重要锚点，为远程增强子功能提供了一般见解。
Recent evidence suggests that long-range enhancers and gene promoters are in close proximity, which might reflect the formation of chromatin loops. Here, we examined the mechanism for DNA looping at the beta-globin locus. By using chromosome conformation capture (3C), we show that the hematopoietic transcription factor GATA-1 and its cofactor FOG-1 are required for the physical interaction between the beta-globin locus control region (LCR) and the beta-major globin promoter. Kinetic studies reveal that GATA-1-induced loop formation correlates with the onset of beta-globin transcription and occurs independently of new protein synthesis. GATA-1 occupies the beta-major globin promoter normally in fetal liver erythroblasts from mice lacking the LCR, suggesting that GATA-1 binding to the promoter and LCR are independent events that occur prior to loop formation. Together, these data demonstrate that GATA-1 and FOG-1 are essential anchors for a tissue-specific chromatin loop, providing general insights into long-range enhancer function.