School of Life Sciences, University of Nevada, Las Vegas, NV 89154, USA.
Nevada Institute of Personalized Medicine, Las Vegas, NV 89154, USA.
Trends Genet. 2022 Jan;38(1):12-21. doi: 10.1016/j.tig.2021.07.007. Epub 2021 Jul 30.
Human specific endogenous retrovirus H (HERVH) is highly expressed in both naive and primed stem cells and is essential for pluripotency. Despite the proven relationship between HERVH expression and pluripotency, there is no single definitive model for the function of HERVH. Instead, several hypotheses of a regulatory function have been put forward including HERVH acting as enhancers, long noncoding RNAs (lncRNAs), and most recently as markers of topologically associating domain (TAD) boundaries. Recently several enhancer-associated lncRNAs have been characterized, which bind to Mediator and are necessary for promoter-enhancer folding interactions. We propose a synergistic model of HERVH function combining relevant findings and discuss the current limitations for its role in regulation, including the lack of evidence for a pluripotency-associated target gene.
人类特异性内源性逆转录病毒 H（HERVH）在幼稚和初始干细胞中均高度表达，对多能性至关重要。尽管 HERVH 表达与多能性之间存在明确的关系，但 HERVH 的功能尚无单一明确的模型。相反，已经提出了几种调节功能的假说，包括 HERVH 作为增强子、长非编码 RNA（lncRNA），以及最近作为拓扑关联域（TAD）边界标记物。最近，已经鉴定出几种与增强子相关的 lncRNA，它们与 Mediator 结合，对于启动子-增强子折叠相互作用是必需的。我们提出了一个 HERVH 功能的协同模型，结合了相关发现，并讨论了其在调控中的作用的当前局限性，包括缺乏与多能性相关的靶基因的证据。
