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Corto与DSP1相互作用并结合到Scr Hox基因的一个维持元件上:了解三胸节和多梳蛋白增强子的作用。

Corto and DSP1 interact and bind to a maintenance element of the Scr Hox gene: understanding the role of Enhancers of trithorax and Polycomb.

作者信息

Salvaing Juliette, Decoville Martine, Mouchel-Vielh Emmanuèle, Bussière Marianne, Daulny Anne, Boldyreva Lidiya, Zhimulev Igor, Locker Daniel, Peronnet Frédérique

机构信息

UMR 7622, CNRS, Université Pierre et Marie Curie, 9, quai Saint-Bernard, 75252 Paris cedex 05, France.

出版信息

BMC Biol. 2006 Apr 14;4:9. doi: 10.1186/1741-7007-4-9.

Abstract

BACKGROUND

Polycomb-group genes (PcG) encode proteins that maintain homeotic (Hox) gene repression throughout development. Conversely, trithorax-group (trxG) genes encode positive factors required for maintenance of long term Hox gene activation. Both kinds of factors bind chromatin regions called maintenance elements (ME). Our previous work has shown that corto, which codes for a chromodomain protein, and dsp1, which codes for an HMGB protein, belong to a class of genes called the Enhancers of trithorax and Polycomb (ETP) that interact with both PcG and trxG. Moreover, dsp1 interacts with the Hox gene Scr, the DSP1 protein is present on a Scr ME in S2 cells but not in embryos. To understand better the role of ETP, we addressed genetic and molecular interactions between corto and dsp1.

RESULTS

We show that Corto and DSP1 proteins co-localize at 91 sites on polytene chromosomes and co-immunoprecipitate in embryos. They interact directly through the DSP1 HMG-boxes and the amino-part of Corto, which contains a chromodomain. In order to search for a common target, we performed a genetic interaction analysis. We observed that corto mutants suppressed dsp11 sex comb phenotypes and enhanced AntpScx phenotypes, suggesting that corto and dsp1 are simultaneously involved in the regulation of Scr. Using chromatin immunoprecipitation of the Scr ME, we found that Corto was present on this ME both in Drosophila S2 cells and in embryos, whereas DSP1 was present only in S2 cells.

CONCLUSION

Our results reveal that the proteins Corto and DSP1 are differently recruited to a Scr ME depending on whether the ME is active, as seen in S2 cells, or inactive, as in most embryonic cells. The presence of a given combination of ETPs on an ME would control the recruitment of either PcG or TrxG complexes, propagating the silenced or active state.

摘要

背景

多梳蛋白家族基因(PcG)编码的蛋白质在整个发育过程中维持同源异型(Hox)基因的抑制状态。相反,三胸蛋白家族(trxG)基因编码维持Hox基因长期激活所需的正向因子。这两类因子都结合称为维持元件(ME)的染色质区域。我们之前的工作表明,编码一个染色质结构域蛋白的corto和编码一个高迁移率族蛋白B(HMGB)的dsp1属于一类称为三胸蛋白和多梳蛋白增强子(ETP)的基因,它们与PcG和trxG都相互作用。此外,dsp1与Hox基因Scr相互作用,DSP1蛋白存在于S2细胞中的Scr ME上,但在胚胎中不存在。为了更好地理解ETP的作用,我们研究了corto和dsp1之间的遗传和分子相互作用。

结果

我们发现Corto和DSP1蛋白在多线染色体上的91个位点共定位,并且在胚胎中共免疫沉淀。它们通过DSP1的HMG盒和Corto的氨基部分直接相互作用,Corto的氨基部分包含一个染色质结构域。为了寻找共同靶点,我们进行了遗传相互作用分析。我们观察到corto突变体抑制了dsp11性梳表型并增强了AntpScx表型,这表明corto和dsp1同时参与Scr的调控。通过对Scr ME进行染色质免疫沉淀,我们发现Corto在果蝇S2细胞和胚胎中的这个ME上都存在,而DSP1仅存在于S2细胞中。

结论

我们的结果表明,根据ME是活跃的(如在S2细胞中所见)还是不活跃的(如在大多数胚胎细胞中所见),Corto和DSP1蛋白被不同地招募到Scr ME上。ME上特定组合的ETP的存在将控制PcG或TrxG复合物的招募,从而维持沉默或活跃状态。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0703/1459216/552ef2efe71c/1741-7007-4-9-1.jpg

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