Looping and interaction between hypersensitive sites in the active β-globin locus
Looping and interaction between hypersensitive sites in the active β-globin locus
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DOI：
10.1016/s1097-2765(02)00781-5
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发表时间：
2002-12-01
期刊：
影响因子：
16
通讯作者：
de Laat, W
中科院分区：
文献类型：
--
作者：
Tolhuis, B;Palstra, RJ;de Laat, W
真核生物的转录可以受到几十个甚至几百个酶的调控。我们表明，这种远程基因调控在体内涉及转录元件之间的空间相互作用，与干预染色质循环。在表达红细胞和非表达脑组织中分析跨越鼠β-珠蛋白基因座的200 kb区域的空间组织。在大脑中，珠蛋白簇采取看似线性的构象。在红系细胞中，基因座控制区（LCR）的超敏位点位于距离活性基因40-60 kb处，与这些基因在空间上非常接近。具有失活球蛋白基因的介入染色质循环出去。此外，两个遥远的超敏感区域参与这些相互作用。我们认为调控元件的聚集是创造和维持活性染色质结构域和调控转录的关键。
Eukaryotic transcription can be regulated over tens or even hundreds of kilobases. We show that such long-range gene regulation in vivo involves spatial interactions between transcriptional elements, with intervening chromatin looping out. The spatial organization of a 200 kb region spanning the murine beta-globin locus was analyzed in expressing erythroid and nonexpressing brain tissue. In brain, the globin cluster adopts a seemingly linear conformation. In erythroid cells the hypersensitive sites of the locus control region (LCR), located 40-60 kb away from the active genes, come in close spatial proximity with these genes. The intervening chromatin with inactive globin genes loops out. Moreover, two distant hypersensitive regions participate in these interactions. We propose that clustering of regulatory elements is key to creating and maintaining active chromatin domains and regulating transcription.