Regulation of endogenous retrovirus-derived regulatory elements by GATA2/3 and MSX2 in human trophoblast stem cells.
Regulation of endogenous retrovirus-derived regulatory elements by GATA2/3 and MSX2 in human trophoblast stem cells.
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GATA2/3 和 MSX2 在人滋养层干细胞中对内源性逆转录病毒衍生调节元件的调节。
DOI：
10.1101/gr.277150.122
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发表时间：
2023-02
期刊：
影响因子：
7
通讯作者：
Sun, Ming-an
中科院分区：
文献类型：
--
作者：
Du, Cui;Jiang, Jing;Li, Yuzhuo;Yu, Miao;Jin, Jian;Chen, Shuai;Fan, Hairui;Macfarlan, Todd S.;Cao, Bin;Sun, Ming-an
胎盘是真兽目哺乳动物中具有特殊表型多样性的器官。最近的证据表明，许多人胎盘增强子是从内源性逆转录病毒（ERV）的谱系特异性插入进化而来的，但其调控的转录因子（TF）在很大程度上仍然是难以捉摸的。在这里，通过首先关注MER 41，一个灵长类动物特异性ERV家族，以前与胎盘和先天免疫相关，我们发现了除了先天免疫TF STAT 1和IRF 1之外，多种关键滋养层TF（GATA 2/3，MSX 2，GRHL 2）的结合基序。ChIP-seq数据的整合证实了GATA 2/3、MSX 2及其相关因子与人滋养层干细胞（TSC）中大多数MER 41衍生增强子的结合。在人TSC中具有组成性活性的MER 41衍生的增强子不同于在干扰素刺激后活化的增强子，干扰素刺激通过相关TF及其亚家族组成的结合来确定。我们进一步证明GATA 2/3和MSX 2与许多其他ERV家族普遍结合-表明它们对ERV衍生增强子的广泛影响。在功能上，MSX 2敲低后许多合胞体滋养层基因的去抑制可能是由来自ERVs的调控元件介导的-这表明ERVs对于介导转录抑制也很重要。总之，本研究的特点ERV衍生的调控元件的调节GATA 2/3，MSX 2，和他们的辅因子在人类TSCs，并提供了机制的见解ERV在人类滋养层调控网络的重要性。
The placenta is an organ with extraordinary phenotypic diversity in eutherian mammals. Recent evidence suggests that numerous human placental enhancers are evolved from lineage-specific insertions of endogenous retroviruses (ERVs), yet the transcription factors (TFs) underlying their regulation remain largely elusive. Here, by first focusing on MER41, a primate-specific ERV family previously linked to placenta and innate immunity, we uncover the binding motifs of multiple crucial trophoblast TFs (GATA2/3, MSX2, GRHL2) in addition to innate immunity TFs STAT1 and IRF1. Integration of ChIP-seq data confirms the binding of GATA2/3, MSX2, and their related factors on the majority of MER41-derived enhancers in human trophoblast stem cells (TSCs). MER41-derived enhancers that are constitutively active in human TSCs are distinct from those activated upon interferon stimulation, which is determined by the binding of relevant TFs and their subfamily compositions. We further demonstrate that GATA2/3 and MSX2 have prevalent binding to numerous other ERV families — indicating their broad impact on ERV-derived enhancers. Functionally, the derepression of many syncytiotrophoblast genes after MSX2 knockdown is likely to be mediated by regulatory elements derived from ERVs — suggesting ERVs are also important for mediating transcriptional repression. Overall, this study characterizes the regulation of ERV-derived regulatory elements by GATA2/3, MSX2, and their cofactors in human TSCs, and provides mechanistic insights into the importance of ERVs in human trophoblast regulatory network.
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DOI：
10.1093/bioinformatics/btr064
发表时间：
2011-04-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Grant CE;Bailey TL;Noble WS
通讯作者：
Noble WS
影响因子：
13.6
作者：
Ito J;Kimura I;Soper A;Coudray A;Koyanagi Y;Nakaoka H;Inoue I;Turelli P;Trono D;Sato K
通讯作者：
Sato K
DOI：
10.1073/pnas.1708341114
发表时间：
2017-11-07
影响因子：
11.1
作者：
Krendl C;Shaposhnikov D;Rishko V;Ori C;Ziegenhain C;Sass S;Simon L;Müller NS;Straub T;Brooks KE;Chavez SL;Enard W;Theis FJ;Drukker M
通讯作者：
Drukker M
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
3.7
作者：
Derrien T;Estellé J;Marco Sola S;Knowles DG;Raineri E;Guigó R;Ribeca P
通讯作者：
Ribeca P