Active endogenous retroviral elements in human pluripotent stem cells play a role in regulating host gene expression.
Active endogenous retroviral elements in human pluripotent stem cells play a role in regulating host gene expression.
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DOI：
10.1093/nar/gkac265
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发表时间：
2022-05-20
影响因子：
14.9
通讯作者：
Jiang, Wei
中科院分区：
文献类型：
--
作者：
Zhang, Tianzhe;Zheng, Ran;Li, Mao;Yan, Chenchao;Lan, Xianchun;Tong, Bei;Lu, Pei;Jiang, Wei
人内源性逆转录病毒，也称为 LTR 元件，可以与转录因子结合，并在不同的生物环境中通过不同的组蛋白修饰进行标记。最近，单个 LTR 或 LTR 的某些亚类（例如 LTR7/HERVH 和 LTR5_Hs/HERVK 家族）已被确定为顺式调控元件。然而，仍有许多LTR元件的功能未知。在这里，我们通过整合人类胚胎干细胞（ESC）中的 98 个 ChIP-seq 数据，剖析了组蛋白修饰的情况和 LTR 的调控图谱，并注释了富集增强子/启动子相关组蛋白标记的活性 LTR。值得注意的是，我们发现 MER57E3 在功能上充当近端调控元件来激活相应的 ZNF 基因。此外，HERVK转录本主要在细胞核中发挥作用，激活邻近基因。由于LTR5_Hs/LTR5与许多早期胚胎特异性转录因子结合，我们进一步研究了不同多能状态下的表达动态。 LTR5_Hs/LTR5/HERVK 在幼稚 ESC 和扩展多能干细胞 (EPSC) 中表现出较高的表达水平。从功能上来说，高活性的LTR5_Hs/LTR5可以作为远端增强子来调节宿主基因。最终，我们的研究不仅提供了人类ESC中LTR的全面调控图谱，还探索了宿主基因组中MER57E3和LTR5_Hs/LTR5的调控模型。
Human endogenous retroviruses, also called LTR elements, can be bound by transcription factors and marked by different histone modifications in different biological contexts. Recently, individual LTR or certain subclasses of LTRs such as LTR7/HERVH and LTR5_Hs/HERVK families have been identified as cis-regulatory elements. However, there are still many LTR elements with unknown functions. Here, we dissected the landscape of histone modifications and regulatory map of LTRs by integrating 98 ChIP-seq data in human embryonic stem cells (ESCs), and annotated the active LTRs enriching enhancer/promoter-related histone marks. Notably, we found that MER57E3 functionally acted as proximal regulatory element to activate respective ZNF gene. Additionally, HERVK transcript could mainly function in nucleus to activate the adjacent genes. Since LTR5_Hs/LTR5 was bound by many early embryo-specific transcription factors, we further investigated the expression dynamics in different pluripotent states. LTR5_Hs/LTR5/HERVK exhibited higher expression level in naïve ESCs and extended pluripotent stem cells (EPSCs). Functionally, the LTR5_Hs/LTR5 with high activity could serve as a distal enhancer to regulate the host genes. Ultimately, our study not only provides a comprehensive regulatory map of LTRs in human ESCs, but also explores the regulatory models of MER57E3 and LTR5_Hs/LTR5 in host genome.
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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
影响因子：
8.8
作者：
Fasching L;Kapopoulou A;Sachdeva R;Petri R;Jönsson ME;Männe C;Turelli P;Jern P;Cammas F;Trono D;Jakobsson J
通讯作者：
Jakobsson J
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
影响因子：
64.5
作者：
Benayoun BA;Pollina EA;Ucar D;Mahmoudi S;Karra K;Wong ED;Devarajan K;Daugherty AC;Kundaje AB;Mancini E;Hitz BC;Gupta R;Rando TA;Baker JC;Snyder MP;Cherry JM;Brunet A
通讯作者：
Brunet A
影响因子：
12.3
作者：
Jansz N;Faulkner GJ
通讯作者：
Faulkner GJ