近日,武汉大学生命科学学院周荣家教授和程汉华教授实验室在减数分裂表观遗传调控方面取得新突破,相关论文“DNA demethylation and USF regulate the meiosis-specific expression of the mouse Miwi”,在线发表于遗传学领域著名学术期刊《PLoS Genetics》(IF:9.543)。两位教授为通讯作者,第一作者为我院博士生侯宇。同时该文章被该杂志选为“Featured Research”论文,引起国内外广泛关注。
该项研究通过转基因小鼠体内甲基化模式(一种表观遗传方式)的研究,建立了探索减数分裂过程及分子细胞学机制的实验模型, 揭示了Miwi基因在减数分裂过程中时空表达的表观遗传调控机制。有助于探索二倍体向单倍体细胞的分化机制,以及认识在不同时期及特定位置的细胞分化过程。为深入探索细胞分化和发育机制提供了重要基础。(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.