Nipped-B, a Drosophila homologue of chromosomal adherins, participates in activation by remote enhancers in the cut and Ultrabithorax genes.
Nipped-B, a Drosophila homologue of chromosomal adherins, participates in activation by remote enhancers in the cut and Ultrabithorax genes.
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Nipped-B 是果蝇染色体粘附蛋白的同源物，参与 cut 和 Ultrabithorax 基因中远程增强子的激活。
DOI：
10.1093/genetics/152.2.577
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发表时间：
1999
期刊：
影响因子：
3.3
通讯作者：
Dorsett,D
中科院分区：
文献类型：
--
作者：
Rollins,RA;Morcillo,P;Dorsett,D
增强子如何能够激活几千个碱基之外的启动子是未知的。被位于启动子85 kb处的剪切基因的翼缘增强子激活，需要几个参与翼缘Notch受体通路的基因，包括扇形、退化、mastermind、Chip和Nipped位点。在这里，我们证明了niped突变破坏了四个基本互补群中的一个或多个：l(2)41Ae, l(2)41Af， Nipped- a和Nipped- b。杂合的Nipped突变改变了翼缘和其他组织中Notch突变体的表型，放大了cut顺式调控区突变对cut表达的影响。Nipped-A和l(2)41Af突变进一步减少翼缘增强子的激活，翼缘增强子部分被小缺失破坏。相反，Nipped-B突变不会减少受损增强子的激活，但会增加增强子和启动子之间吉普赛转座子插入的抑制作用。Nipped-B突变也放大了“超胸腔”基因中吉普赛插入的影响。Gypsy结合毛翼绝缘子蛋白抑制因子[Su(Hw)]，阻断增强子-启动子通讯。在Nipped-B突变体中，Su（Hw）增加的绝缘表明Nipped-B产物在结构上促进了增强子-启动子的通信。与这一观点相一致的是，niped - b蛋白与染色体粘附蛋白家族同源，在姐妹染色单体内聚、染色体凝聚和DNA修复中发挥着广泛的作用。
How enhancers are able to activate promoters located several kilobases away is unknown. Activation by the wing margin enhancer in the cut gene, located 85 kb from the promoter, requires several genes that participate in the Notch receptor pathway in the wing margin, including scalloped, vestigial, mastermind, Chip, and the Nipped locus. Here we show that Nipped mutations disrupt one or more of four essential complementation groups: l(2)41Ae, l(2)41Af, Nipped-A, and Nipped-B. Heterozygous Nipped mutations modify Notch mutant phenotypes in the wing margin and other tissues, and magnify the effects that mutations in the cis regulatory region of cut have on cut expression. Nipped-A and l(2)41Af mutations further diminish activation by a wing margin enhancer partly impaired by a small deletion. In contrast, Nipped-B mutations do not diminish activation by the impaired enhancer, but increase the inhibitory effect of a gypsy transposon insertion between the enhancer and promoter. Nipped-B mutations also magnify the effect of a gypsy insertion in the Ultrabithorax gene. Gypsy binds the Suppressor of Hairy-wing insulator protein [Su(Hw)] that blocks enhancer-promoter communication. Increased insulation by Su(Hw) in Nipped-B mutants suggests that Nipped-B products structurally facilitate enhancer-promoter communication. Compatible with this idea, Nipped-B protein is homologous to a family of chromosomal adherins with broad roles in sister chromatid cohesion, chromosome condensation, and DNA repair.