Salvaing Juliette, Nagel Anja C, Mouchel-Vielh Emmanuèle, Bloyer Sébastien, Maier Dieter, Preiss Anette, Peronnet Frédérique
Laboratoire de Biologie du Développement, UMR 7622, Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie-Paris 6, Paris, France.
PLoS One. 2008 Feb 20;3(2):e1658. doi: 10.1371/journal.pone.0001658.
Polycomb (PcG) and trithorax (trxG) genes encode proteins involved in the maintenance of gene expression patterns, notably Hox genes, throughout development. PcG proteins are required for long-term gene repression whereas TrxG proteins are positive regulators that counteract PcG action. PcG and TrxG proteins form large complexes that bind chromatin at overlapping sites called Polycomb and Trithorax Response Elements (PRE/TRE). A third class of proteins, so-called "Enhancers of Trithorax and Polycomb" (ETP), interacts with either complexes, behaving sometimes as repressors and sometimes as activators. The role of ETP proteins is largely unknown.
METHODOLOGY/PRINCIPAL FINDINGS: In a two-hybrid screen, we identified Cyclin G (CycG) as a partner of the Drosophila ETP Corto. Inactivation of CycG by RNA interference highlights its essential role during development. We show here that Corto and CycG directly interact and bind to each other in embryos and S2 cells. Moreover, CycG is targeted to polytene chromosomes where it co-localizes at multiple sites with Corto and with the PcG factor Polyhomeotic (PH). We observed that corto is involved in maintaining Abd-B repression outside its normal expression domain in embryos. This could be achieved by association between Corto and CycG since both proteins bind the regulatory element iab-7 PRE and the promoter of the Abd-B gene.
CONCLUSIONS/SIGNIFICANCE: Our results suggest that CycG could regulate the activity of Corto at chromatin and thus be involved in changing Corto from an Enhancer of TrxG into an Enhancer of PcG.
多梳(PcG)基因和三胸节(trxG)基因编码参与在整个发育过程中维持基因表达模式的蛋白质,尤其是同源异型(Hox)基因。PcG蛋白是长期基因抑制所必需的,而TrxG蛋白是对抗PcG作用的正向调节因子。PcG和TrxG蛋白形成大的复合物,它们在称为多梳和三胸节反应元件(PRE/TRE)的重叠位点结合染色质。第三类蛋白质,即所谓的“三胸节和多梳增强子”(ETP),与这两种复合物相互作用,有时表现为抑制因子,有时表现为激活因子。ETP蛋白的作用在很大程度上尚不清楚。
方法/主要发现:在双杂交筛选中,我们鉴定出细胞周期蛋白G(CycG)是果蝇ETP蛋白Corto的一个相互作用蛋白。通过RNA干扰使CycG失活突出了其在发育过程中的重要作用。我们在此表明,Corto和CycG在胚胎和S2细胞中直接相互作用并彼此结合。此外,CycG定位于多线染色体,在那里它与Corto以及PcG因子多同源异型(PH)在多个位点共定位。我们观察到,Corto参与在胚胎中维持Abd - B在其正常表达域之外的抑制状态。这可能是通过Corto和CycG之间的结合实现的,因为这两种蛋白都结合调控元件iab - 7 PRE和Abd - B基因的启动子。
结论/意义:我们的结果表明,CycG可能在染色质上调节Corto的活性,从而参与将Corto从TrxG的增强子转变为PcG的增强子。