生物
内源性逆转录病毒
增强子
滋养层
合胞体
基因表达调控
西斯特
遗传学
细胞生物学
基因
胎盘
基因组
基因表达
X-失活
细胞
胎儿
X染色体
怀孕
作者
Miao Yu,Xinning Hu,Zihang Pan,Chunfang Du,Jing Jiang,Wan-Shan Zheng,Han Cai,Yinan Wang,Wenbo Deng,Haibin Wang,Jinhua Lu,Miao‐Kun Sun,Bin Cao
摘要
Abstract Endogenous retroviruses (ERVs) have been proposed as a driving force for the evolution of the mammalian placenta, however, the contribution of ERVs to placental development and the underlying regulatory mechanism remain largely elusive. A key process of placental development is the formation of multinucleated syncytiotrophoblasts (STBs) in direct contact with maternal blood, through which constitutes the maternal-fetal interface critical for nutrient allocation, hormone production and immunological modulation during pregnancy. We delineate that ERVs profoundly rewire the transcriptional program of trophoblast syncytialization. Here, we first determined the dynamic landscape of bivalent ERV-derived enhancers with dual occupancy of H3K27ac and H3K9me3 in human trophoblast stem cells (hTSCs). We further demonstrated that enhancers overlapping several ERV families tend to exhibit increased H3K27ac and reduced H3K9me3 occupancy in STBs relative to hTSCs. Particularly, bivalent enhancers derived from the Simiiformes-specific MER50 transposons were linked to a cluster of genes important for STB formation. Importantly, deletions of MER50 elements adjacent to several STB genes, including MFSD2A and TNFAIP2, significantly attenuated their expression concomitant to compromised syncytium formation. Together, we propose that ERV-derived enhancers, MER50 specifically, fine-tune the transcriptional networks accounting for human trophoblast syncytialization, which sheds light on a novel ERV-mediated regulatory mechanism underlying placental development.
科研通智能强力驱动
Strongly Powered by AbleSci AI