Human reproduction is regulated by retrotransposons derived from ancient Hominidae-specific viral infections.
Human reproduction is regulated by retrotransposons derived from ancient Hominidae-specific viral infections.
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DOI：
10.1038/s41467-022-28105-1
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发表时间：
2022-01-24
影响因子：
16.6
通讯作者：
Clark AT
中科院分区：
文献类型：
--
作者：
Xiang X;Tao Y;DiRusso J;Hsu FM;Zhang J;Xue Z;Pontis J;Trono D;Liu W;Clark AT
生殖细胞是将DNA从一代传递到下一代所必需的。在人类生殖过程中，生殖细胞的发育始于原始生殖细胞（PGCs）的特化，而不能特化PGCs会导致人类不育。最近的研究表明，PGC特化所需的转录因子网络在哺乳动物中已经分化，这对我们理解人类生殖产生了重大影响。在这里，我们揭示了人科特异性转座因子（TE）LTR5H，可以作为TEENhancers（TE嵌入式增强器），以促进PGC的规范。LTR5H TEENhancer在体内和体外PGC特化过程中变得转录活性，表观遗传重编程导致染色质可及性增加、局部DNA去甲基化、H3K27ac富集和关键hPGC转录因子的占据。用KRAB介导的CRISPRi灭活LTR5H TEENhancer对生殖细胞特化具有显著影响。总之，我们的数据揭示了人科特异性LTR 5 HS TEENhancer在人类生殖细胞发育中的重要作用。原始生殖细胞（PGC）特化所需的转录因子网络已知在哺乳动物中发散。在这里，作者表明，人科特异性转座因子（TE）LTR5H在PGC特化过程中变得转录活性，LTR5H失活废除了人类PGC特化
Germ cells are essential to pass DNA from one generation to the next. In human reproduction, germ cell development begins with the specification of primordial germ cells (PGCs) and a failure to specify PGCs leads to human infertility. Recent studies have revealed that the transcription factor network required for PGC specification has diverged in mammals, and this has a significant impact on our understanding of human reproduction. Here, we reveal that the Hominidae-specific Transposable Elements (TEs) LTR5Hs, may serve as TEENhancers (TE Embedded eNhancers) to facilitate PGC specification. LTR5Hs TEENhancers become transcriptionally active during PGC specification both in vivo and in vitro with epigenetic reprogramming leading to increased chromatin accessibility, localized DNA demethylation, enrichment of H3K27ac, and occupation of key hPGC transcription factors. Inactivation of LTR5Hs TEENhancers with KRAB mediated CRISPRi has a significant impact on germ cell specification. In summary, our data reveals the essential role of Hominidae-specific LTR5Hs TEENhancers in human germ cell development. The transcription factor network required for primordial germ cell (PGC) specification is known to diverge in mammals. Here the authors show that hominidae-specific transposable element (TE) LTR5Hs becomes transcriptionally active during PGC specification, and LTR5Hs inactivation abrogates human PGC specification
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影响因子：
14.9
作者：
Howe KL;Achuthan P;Allen J;Allen J;Alvarez-Jarreta J;Amode MR;Armean IM;Azov AG;Bennett R;Bhai J;Billis K;Boddu S;Charkhchi M;Cummins C;Da Rin Fioretto L;Davidson C;Dodiya K;El Houdaigui B;Fatima R;Gall A;Garcia Giron C;Grego T;Guijarro-Clarke C;Haggerty L;Hemrom A;Hourlier T;Izuogu OG;Juettemann T;Kaikala V;Kay M;Lavidas I;Le T;Lemos D;Gonzalez Martinez J;Marugán JC;Maurel T;McMahon AC;Mohanan S;Moore B;Muffato M;Oheh DN;Paraschas D;Parker A;Parton A;Prosovetskaia I;Sakthivel MP;Salam AIA;Schmitt BM;Schuilenburg H;Sheppard D;Steed E;Szpak M;Szuba M;Taylor K;Thormann A;Threadgold G;Walts B;Winterbottom A;Chakiachvili M;Chaubal A;De Silva N;Flint B;Frankish A;Hunt SE;IIsley GR;Langridge N;Loveland JE;Martin FJ;Mudge JM;Morales J;Perry E;Ruffier M;Tate J;Thybert D;Trevanion SJ;Cunningham F;Yates AD;Zerbino DR;Flicek P
通讯作者：
Flicek P
影响因子：
64.5
作者：
Gkountela S;Zhang KX;Shafiq TA;Liao WW;Hargan-Calvopiña J;Chen PY;Clark AT
通讯作者：
Clark AT
影响因子：
3.3
作者：
Fuchs NV;Loewer S;Daley GQ;Izsvák Z;Löwer J;Löwer R
通讯作者：
Löwer R
人类原始生殖细胞的转录组和 DNA 甲基化组景观
影响因子：
64.5
作者：
Guo, Fan;Yan, Liying;Qiao, Jie
通讯作者：
Qiao, Jie
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