近日,，武漢大學(xué)生命科學(xué)學(xué)院周榮家教授和程漢華教授實(shí)驗(yàn)室在減數(shù)分裂表觀遺傳調(diào)控方面取得新突破,，相關(guān)論文“DNA demethylation and USF regulate the meiosis-specific expression of the mouse Miwi”，在線發(fā)表于遺傳學(xué)領(lǐng)域著名學(xué)術(shù)期刊《PLoS Genetics》（IF：9.543）,。兩位教授為通訊作者,，第一作者為我院博士生侯宇。同時(shí)該文章被該雜志選為“Featured Research”論文,，引起國(guó)內(nèi)外廣泛關(guān)注,。
該項(xiàng)研究通過(guò)轉(zhuǎn)基因小鼠體內(nèi)甲基化模式（一種表觀遺傳方式）的研究，建立了探索減數(shù)分裂過(guò)程及分子細(xì)胞學(xué)機(jī)制的實(shí)驗(yàn)?zāi)Ｐ停?揭示了Miwi基因在減數(shù)分裂過(guò)程中時(shí)空表達(dá)的表觀遺傳調(diào)控機(jī)制,。有助于探索二倍體向單倍體細(xì)胞的分化機(jī)制,，以及認(rèn)識(shí)在不同時(shí)期及特定位置的細(xì)胞分化過(guò)程。為深入探索細(xì)胞分化和發(fā)育機(jī)制提供了重要基礎(chǔ),。（生物谷Bioon.com）
doi:10.1371/journal.pgen.1002716
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DNA Demethylation and USF Regulate the Meiosis-Specific Expression of the Mouse Miwi
Yu Hou, Jia Yuan, Xiang Zhou, Xiazhou Fu, Hanhua Cheng*, Rongjia Zhou*
Miwi, a member of the Argonaute family, is required for initiating spermiogenesis; however, the mechanisms that regulate the expression of the Miwi gene remain unknown. By mutation analysis and transgenic models, we identified a 303 bp proximal promoter region of the mouse Miwi gene, which controls specific expression from midpachytene spermatocytes to round spermatids during meiosis. We characterized the binding sites of transcription factors NF-Y (Nuclear Factor Y) and USF (Upstream Stimulatory Factor) within the core promoter and found that both factors specifically bind to and activate the Miwi promoter. Methylation profiling of three CpG islands within the proximal promoter reveals a markedly inverse correlation between the methylation status of the CpG islands and germ cell type–specific expression of Miwi. CpG methylation at the USF–binding site within the E2 box in the promoter inhibits the binding of USF. Transgenic Miwi-EGFP and endogenous Miwi reveal a subcellular co-localization pattern in the germ cells of the Miwi-EGFP transgenic mouse. Furthermore, the DNA methylation profile of the Miwi promoter–driven transgene is consistent with that of the endogenous Miwi promoter, indicating that Miwi transgene is epigenetically modified through methylation in vivo to ensure its spatio-temporal expression. Our findings suggest that USF controls Miwi expression from midpachytene spermatocytes to round spermatids through methylation-mediated regulation. This work identifies an epigenetic regulation mechanism for the spatio-temporal expression of mouse Miwi during spermatogenesis.
