蜕膜化
间质细胞
表观遗传学
细胞生物学
生物
染色质
DNA甲基化
蜕膜细胞
染色质重塑
癌症研究
遗传学
基因表达
胎盘
基因
胎儿
怀孕
作者
Mengying Liu,Wenbo Deng,Lu Tang,Meng Liu,Haili Bao,Chuanhui Guo,Chang Zhang,Jinhua Lu,Haibin Wang,Zhongxian Lu,Shuangbo Kong
标识
DOI:10.1038/s41467-022-28657-2
摘要
Abstract During decidualization in rodents, uterine stroma undergoes extensive reprograming into distinct cells, forming the discrete regions defined as the primary decidual zone (PDZ), the secondary decidual zone (SDZ) and the layer of undifferentiated stromal cells respectively. Here we show that uterine deletion of Men1 , a member of the histone H3K4 methyltransferase complex, disrupts the terminal differentiation of stroma, resulting in chaotic decidualization and pregnancy failure. Genome-wide epigenetic profile reveals that Men1 binding in chromatin recapitulates H3K4me3 distribution. Further transcriptomic investigation demonstrates that Men1 directly regulates the expression of PTX3, an extra-cellular trap for FGF2 in decidual cells. Decreased Ptx3 upon Men1 ablation leads to aberrant activation of ERK1/2 in the SDZ due to the unrestrained FGF2 signal emanated from undifferentiated stromal cells, which blunt BMP2 induction and decidualization. In brief, our study provides genetic and molecular mechanisms for epigenetic rewiring mediated decidual regionalization by Men1 and sheds new light on pregnancy maintenance.
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