Endogenous retrovirus-derived enhancers confer the transcriptional regulation of human trophoblast syncytialization.
Endogenous retrovirus-derived enhancers confer the transcriptional regulation of human trophoblast syncytialization.
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内源性逆转录病毒衍生的增强子赋予人滋养层合胞化的转录调节
DOI：
10.1093/nar/gkad109
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发表时间：
2023-06-09
影响因子：
14.9
通讯作者：
中科院分区：
文献类型：
--
作者：
摘要内源性逆转录病毒（ERVs）被认为是哺乳动物胎盘进化的驱动力，然而，ERVs对胎盘发育的作用及其调控机制仍不清楚。胎盘发育的一个关键过程是与母体血液直接接触的多核合胞体滋养层（STB）的形成，通过其构成妊娠期间营养分配、激素产生和免疫调节的关键母胎界面。我们描绘ERVs深刻地重新布线滋养细胞合胞化的转录程序。在这里，我们首先确定了在人滋养层干细胞（hTSCs）中具有H3K27ac和H3K9me3双重占用的二价ERV衍生的增强子的动态景观。我们进一步证明了与几个ERV家族重叠的增强子倾向于在STB中相对于hTSC表现出增加的H3K27ac和减少的H3K9me3占据。特别地，衍生自Simiiformes特异性MER 50转座子的二价增强子与STB形成重要的基因簇连接。重要的是，与几个STB基因（包括MFSD 2A和TNFAIP 2）相邻的MER 50元件的缺失显着减弱了它们的表达，同时损害了合胞体形成。总之，我们建议ERV衍生的增强子，MER50具体，微调的转录网络占人类滋养层合胞，揭示了一种新的ERV介导的调节机制，胎盘发育的基础。
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.
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影响因子：
7.7
作者：
Deb S;Felix DA;Koch P;Deb MK;Szafranski K;Buder K;Sannai M;Groth M;Kirkpatrick J;Pietsch S;Gollowitzer A;Groß A;Riemenschneider P;Koeberle A;González-Estévez C;Rudolph KL
通讯作者：
Rudolph KL
DOI：
10.1126/science.aad5497
发表时间：
2016-03-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Chuong EB;Elde NC;Feschotte C
通讯作者：
Feschotte C
影响因子：
30.8
作者：
Chuong, Edward B.;Rumi, M. A. Karim;Soares, Michael J.;Baker, Julie C.
通讯作者：
Baker, Julie C.
影响因子：
5.2
作者：
Dittmar T;Weiler J;Luo T;Hass R
通讯作者：
Hass R
DOI：
10.1073/pnas.1112304108
发表时间：
2011-11-15
影响因子：
11.1
作者：
Dupressoir, Anne;Vernochet, Cecile;Heidmann, Thierry
通讯作者：
Heidmann, Thierry