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在果蝇胚胎中,将背侧介导的激活与背侧介导的抑制解偶联。

Uncoupling dorsal-mediated activation from dorsal-mediated repression in the Drosophila embryo.

作者信息

Ratnaparkhi Girish S, Jia Songtao, Courey Albert J

机构信息

Department of Chemistry and Biochemistry, University of California at Los Angeles, Los Angeles, CA 90095-1569, USA.

出版信息

Development. 2006 Nov;133(22):4409-14. doi: 10.1242/dev.02643. Epub 2006 Oct 11.

Abstract

The Rel family transcription factor Dorsal patterns the dorsoventral axis of the Drosophila embryo by activating genes such as twist and snail and repressing genes such as decapentaplegic and zerknüllt. Dorsal represses transcription by recruiting the co-repressor Groucho. However, repression occurs only when Dorsal-binding sites are close to binding sites for other factors that also bind Groucho. The need for additional factors to assist Dorsal in repression may result from the intrinsically weak interaction between Dorsal and Groucho. To test this idea, we generated a Dorsal variant containing a high-affinity Groucho recruitment motif at its C terminus. As predicted, this variant functions as a dedicated repressor, silencing decapentaplegic and zerknüllt while failing to activate twist and snail. We also converted Dorsal into a dedicated activator by replacing its weak Groucho-recruitment motif with heterologous activation domains. Although the dedicated activator alleles fail to repress decapentaplegic and zerknüllt in the syncytial blastoderm embryo, they are able to pattern the dorsoventral axis. This indicates that dorsoventral patterning is not dependent upon Dorsal-mediated repression, reflecting the existence of redundant mechanisms to block Decapentaplegic signaling.

摘要

Rel家族转录因子背腹因子通过激活如twist和snail等基因以及抑制如decapentaplegic和zerknüllt等基因来调控果蝇胚胎的背腹轴。背腹因子通过招募共抑制因子Groucho来抑制转录。然而,只有当背腹因子结合位点靠近其他也能结合Groucho的因子的结合位点时,抑制作用才会发生。背腹因子在抑制过程中需要其他因子协助,这可能是由于背腹因子与Groucho之间内在的弱相互作用所致。为了验证这一想法,我们构建了一个在其C末端含有高亲和力Groucho招募基序的背腹因子变体。正如预期的那样,这个变体起到了专一性抑制因子的作用,使decapentaplegic和zerknüllt沉默,同时无法激活twist和snail。我们还通过用异源激活结构域替换其弱的Groucho招募基序,将背腹因子转化为专一性激活因子。尽管这些专一性激活因子等位基因在合胞体胚盘胚胎中无法抑制decapentaplegic和zerknüllt,但它们能够调控背腹轴。这表明背腹轴的形成并不依赖于背腹因子介导的抑制作用,这反映了存在冗余机制来阻断Decapentaplegic信号传导。

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