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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Activity regulation of Hox proteins, a mechanism for altering functional specificity in development and evolution
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Activity regulation of Hox proteins, a mechanism for altering functional specificity in development and evolution

机译:Hox蛋白的活性调节,一种改变发育和进化中功能特异性的机制

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摘要

The closely related Hox transcription factors Ultrabithorax (Ubx) and Antennapedia (Antp) respectively direct first abdominal (A1) and second thoracic (T2) segment identities in Drosophila. It has been proposed that their functional differences derive from their differential occu- pancy of DNA target sites. Here we show that a hybrid version of Ubx (Ubx-VP16), which possesses an enhanced transcrip- tional activation function, no longer directs A1 denticle pat- tern in embryonic epidermal cells. Instead, it mimics Antp in directing T2 denticle pattern, and it can rescue the cuticular loss-of-function phenotype of Antp mutants. In cells that do not produce denticles, Ubx-VP16 appears to have largely retained its normal repressive regulatory functions. These results suggest that the modulation of Hox activation and repression functions can account for segment-specific mor- phological differences that are controlled by different mem- bers of the Hox family. Our results also are consistent with the idea that activity regulation underlies the phenotypic suppres- sion phenomenon in which a more posterior Hox protein suppresses the function of a more anterior member of the Hox cluster. The acquisition of novel activation and repression potentials in Hox proteins may be an important mechanism underlying the generation of subtle morphological differences during evolution.
机译:密切相关的Hox转录因子Ultrabithorax(Ubx)和Antennapedia(Antp)分别指导果蝇中的第一腹部(A1)和第二胸部(T2)段身份。有人提出,它们的功能差异源于它们对DNA靶位点的不同占有率。在这里,我们显示了具有增强的转录激活功能的Ubx的混合版本(Ubx-VP16),不再在胚胎表皮细胞中指导A1牙质模式。相反,它可以模拟Antp来指导T2牙菌斑模式,并且可以挽救Antp突变体的表皮功能丧失表型。在不产生细粒的细胞中,Ubx-VP16似乎在很大程度上保留了其正常的抑制调节功能。这些结果表明,Hox激活和抑制功能的调节可以解释由Hox家族的不同成员控制的节段特异性形态学差异。我们的结果也与以下观点一致:活动调节是表型抑制现象的基础,在这种现象中,后部的Hox蛋白抑制了Hox簇中的前部成员的功能。 Hox蛋白中新的激活和抑制潜力的获取可能是进化过程中细微形态差异产生的重要机制。

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