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The interaction between the coactivator dCBP and Modulo a chromatin-associated factor affects segmentation and melanotic tumor formation in Drosophila

机译:辅助激活剂dCBP与染色质相关因子Modulo之间的相互作用会影响果蝇的节段和黑色素瘤形成

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摘要

The development of Drosophila requires the function of the CREB-binding protein, dCBP. In flies, dCBP serves as a coactivator for the transcription factors Cubitus interruptus, Dorsal, and Mad, and as a cosuppressor of Drosophila T cell factor. Current models propose that CBP, through its intrinsic and associated histone acetyltransferase activities, affects transient chromatin changes that allow the preinitiation complex to access the promoter. In this report, we provide evidence that dCBP may regulate the formation of chromatin states through interactions with the modulo (mod) gene product, a protein that is thought to be involved in chromatin packaging. We demonstrate that dCBP and Modulo bind in vitro and in vivo, that mutations in mod enhance the embryonic phenotype of a dCBP mutation, and that dCBP mutations enhance the melanotic tumor phenotype characteristic of mod homozygous mutants. These results imply that, in addition to its histone acetyltransferase activity, dCBP may affect higher-order chromatin structure.
机译:果蝇的发育需要CREB结合蛋白dCBP的功能。在果蝇中,dCBP可以作为转录因子Cubitus interruptus,Dorsal和Mad的共激活因子,并作为果蝇T细胞因子的共抑制因子。当前的模型提出,CBP通过其固有的和相关的组蛋白乙酰转移酶活性,影响瞬时染色质变化,从而使预起始复合物能够进入启动子。在本报告中,我们提供了证据,证明dCBP可能通过与模(mod)基因产物(一种可能参与染色质包装的蛋白质)相互作用来调节染色质状态的形成。我们证明了dCBP和Modulo在体外和体内结合,mod中的突变增强了dCBP突变的胚胎表型,并且dCBP突变增强了mod纯合突变体的黑素瘤肿瘤表型。这些结果表明,除了其组蛋白乙酰转移酶活性外,dCBP还可能影响高级染色质结构。

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