The Drosophila insulator proteins CTCF and CP190 link enhancer blocking to body patterning
The Drosophila insulator proteins CTCF and CP190 link enhancer blocking to body patterning
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DOI：
10.1038/sj.emboj.7601851
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发表时间：
2007-10-03
期刊：
影响因子：
11.4
通讯作者：
Renkawitz, Rainer
中科院分区：
文献类型：
--
作者：
Mohan, Man;Bartkuhn, Marek;Renkawitz, Rainer
绝缘子序列通过阻断不适当的相互作用将远距离定位的增强子元件的功能引导到适当的靶基因。在果蝇中，已经鉴定了五种不同的绝缘子结合蛋白，Zw 5、BEAF-32、GAGA因子、Su（Hw）和dCTCF。只有dCTCF在脊椎动物中具有已知的保守对应物。在这里，我们发现结构相关的因子dCTCF和Su（Hw）具有不同的结合靶点。相反，Su（Hw）相互作用因子CP 190与dCTCF结合位点大部分重叠，并与dCTCF相互作用。dCTCF与靶标的结合在许多情况下需要CP 190，而其他情况下不依赖于CP 190。对双胸复合物的分析表明，旁片段特异性调节结构域之间的六个边界在体内与dCTCF和CP 190结合。dCTCF无效突变影响Abdominal-B的表达，导致噬菌体致死和同源异型表型。在幼虫发育过程中dCTCF表达的短脉冲挽救了dCTCF功能丧失表型。总之，我们证明了dCTCF在苍蝇发育和腹部分割的调节中的重要性。
Insulator sequences guide the function of distantly located enhancer elements to the appropriate target genes by blocking inappropriate interactions. In Drosophila, five different insulator binding proteins have been identified, Zw5, BEAF-32, GAGA factor, Su(Hw) and dCTCF. Only dCTCF has a known conserved counterpart in vertebrates. Here we find that the structurally related factors dCTCF and Su(Hw) have distinct binding targets. In contrast, the Su(Hw) interacting factor CP190 largely overlapped with dCTCF binding sites and interacts with dCTCF. Binding of dCTCF to targets requires CP190 in many cases, whereas others are independent of CP190. Analysis of the bithorax complex revealed that six of the borders between the parasegment specific regulatory domains are bound by dCTCF and by CP190 in vivo. dCTCF null mutations affect expression of Abdominal-B, cause pharate lethality and a homeotic phenotype. A short pulse of dCTCF expression during larval development rescues the dCTCF loss of function phenotype. Overall, we demonstrate the importance of dCTCF in fly development and in the regulation of abdominal segmentation.