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科学研究
20220422 Active endogenous retroviral elements in human pluripotent stem cells play a role in regulating host gene expression
发布时间:2022-04-25  来源:  阅读次数:

Tianzhe Zhang, Ran Zheng, Mao Li, ‍Chenchao Yan, Xianchun Lan,  Bei Tong, Pei Lu, Wei Jiang (2022). Active endogenous retroviral elements in human pluripotent stem cells play a role in regulating host gene expression. Nucleic Acids Res. (蒋卫)


Abstract

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.


原文链接:

https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkac265/6572368



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