当前位置: X-MOL 学术G3 Genes Genomes Genet. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Maintenance of Cell Fate by the Polycomb Group Gene Sex Combs Extra Enables a Partial Epithelial Mesenchymal Transition in Drosophila
G3: Genes, Genomes, Genetics ( IF 2.6 ) Pub Date : 2020-12-01 , DOI: 10.1534/g3.120.401785
Grace Jefferies 1 , Jason Somers 1 , Isabelle Lohrey 1 , Vishal Chaturvedi 1 , Jacob Calabria 1 , Owen J Marshall 2 , Tony D Southall 3 , Robert Saint 1 , Michael J Murray 1
Affiliation  

Epigenetic silencing by Polycomb group (PcG) complexes can promote epithelial-mesenchymal transition (EMT) and stemness and is associated with malignancy of solid cancers. Here we report a role for Drosophila PcG repression in a partial EMT event that occurs during wing disc eversion, an early event during metamorphosis. In a screen for genes required for eversion we identified the PcG genes Sex combs extra (Sce) and Sex combs midleg (Scm). Depletion of Sce or Scm resulted in internalized wings and thoracic clefts, and loss of Sce inhibited the EMT of the peripodial epithelium and basement membrane breakdown, ex vivo. Targeted DamID (TaDa) using Dam-Pol II showed that Sce knockdown caused a genomic transcriptional response consistent with a shift toward a more stable epithelial fate. Surprisingly only 17 genes were significantly upregulated in Sce-depleted cells, including Abd-B, abd-A, caudal, and nubbin. Each of these loci were enriched for Dam-Pc binding. Of the four genes, only Abd-B was robustly upregulated in cells lacking Sce expression. RNAi knockdown of all four genes could partly suppress the Sce RNAi eversion phenotype, though Abd-B had the strongest effect. Our results suggest that in the absence of continued PcG repression peripodial cells express genes such as Abd-B, which promote epithelial state and thereby disrupt eversion. Our results emphasize the important role that PcG suppression can play in maintaining cell states required for morphogenetic events throughout development and suggest that PcG repression of Hox genes may affect epithelial traits that could contribute to metastasis.



中文翻译:

通过多梳基团基因性梳的细胞命运维持额外使果蝇部分上皮间质过渡。

Polycomb组(PcG)复合物的表观遗传沉默可以促进上皮-间质转化(EMT)和干性,并与实体癌的恶性肿瘤相关。在这里,我们报告果蝇PcG抑制作用在翼盘外翻期间发生的部分EMT事件中的作用,这是变态期间的早期事件。在筛选外翻所需基因的过程中,我们确定了PcG基因性梳额外Sce)和性梳中腿(Scm)SceScm的耗竭导致内翼和胸腔内left以及Sce的丧失抑制离体时周膜上皮的EMT和基底膜分解。使用Dam-Pol II靶向DamID(TaDa)显示,Sce抑制导致基因组转录反应,与向更稳定的上皮命运转移一致。令人惊讶的,只有17个基因上调显著在SCE耗尽的细胞,包括阿卜杜勒-B ABD-A 尾部,和片体。这些基因座中的每一个都富集了Dam-Pc结合。在这四个基因中,只有Abd-B在缺乏Sce表达的细胞中强烈上调。尽管所有四个基因的RNAi敲除可以部分抑制Sce RNAi外表型Abd-B作用最强。我们的结果表明,在没有持续的PcG抑制的情况下,周膜细胞表达的基因如Abd-B会促进上皮状态并从而破坏外翻。我们的结果强调了PcG抑制在维持整个发育过程中形态发生事件所需的细胞状态中可以发挥的重要作用,并表明Hox基因的PcG抑制可能影响上皮性状,从而可能导致转移。

更新日期:2020-12-03
down
wechat
bug