Endogenous retroviruses function as species-specific enhancer elements in the placenta.
Endogenous retroviruses function as species-specific enhancer elements in the placenta.
复制标题
DOI：
10.1038/ng.2553
复制
发表时间：
2013-03
期刊：
影响因子：
30.8
通讯作者：
Baker, Julie C.
中科院分区：
文献类型：
--
作者：
Chuong, Edward B.;Rumi, M. A. Karim;Soares, Michael J.;Baker, Julie C.
哺乳动物的胎盘在不同物种之间非常不同，这表明了一段快速进化多样化的历史。为了深入了解胎盘进化的分子驱动因素，我们比较了小鼠和大鼠滋养层干细胞(TSCs)之间生物化学预测的增强子，发现物种特异性增强子在全基因组水平上高度富含内源性逆转录病毒(ERV)。其中一个ERV家族，RLTR13D5，贡献了数百个小鼠特异的H3K4me1/H3K27ac定义的增强子，这些增强子功能上结合了CDX2、eome和ELF5-定义TSC调控网络的核心因子。此外，我们还证明了RLTR13D5能够驱动大鼠胎盘细胞的基因表达。与其他组织的比较表明，物种特异性ERV增强子的活性通常限于低甲基化的组织，这表明允许ERV活性的组织获得了原本沉默的调节变异来源。总体而言，我们的结果暗示ERV增强子共选是胎盘发育显著进化多样化的基础机制。
The mammalian placenta is remarkably distinct between species, suggesting a history of rapid evolutionary diversification. To gain insight into the molecular drivers of placental evolution, we compared biochemically predicted enhancers between mouse and rat trophoblast stem cells (TSCs) and find that species-specific enhancers are highly enriched for endogenous retroviruses (ERVs) on a genome-wide level. One of these ERV families, RLTR13D5, contributes hundreds of mouse-specific H3K4me1/H3K27ac-defined enhancers that functionally bind Cdx2, Eomes, and Elf5 - core factors that define the TSC regulatory network. Furthermore, we demonstrate that RLTR13D5 is capable of driving gene expression in rat placental cells. Comparison with other tissues revealed that species-specific ERV enhancer activity is generally restricted to hypomethylated tissues, suggesting that tissues permissive to ERV activity gain access to an otherwise silenced source of regulatory variation. Overall, our results implicate ERV enhancer cooption as a mechanism underlying the striking evolutionary diversification of placental development.
登录
查看更多内容
影响因子：
3.8
作者：
Enders, A. C.
通讯作者：
Enders, A. C.
影响因子：
30.8
作者：
He, Housheng Hansen;Meyer, Clifford A.;Shin, Hyunjin;Bailey, Shannon T.;Wei, Gang;Wang, Qianben;Zhang, Yong;Xu, Kexin;Ni, Min;Lupien, Mathieu;Mieczkowski, Piotr;Lieb, Jason D.;Zhao, Keji;Brown, Myles;Liu, X. Shirley
通讯作者：
Liu, X. Shirley
影响因子：
21.3
作者：
Ng, Ray Kit;Dean, Wendy;Dawson, Claire;Lucifero, Diana;Madeja, Zofia;Reik, Wolf;Hemberger, Myriam
通讯作者：
Hemberger, Myriam
影响因子：
1.7
作者：
Prudhomme, S;Bonnaud, B;Mallet, F
通讯作者：
Mallet, F
影响因子：
64.5
作者：
Niwa, H;Toyooka, T;Rossant, J
通讯作者：
Rossant, J