Genome Editing Innovation Center, Hiroshima University, 3-10-23 Kagamiyama, Higashi-Hiroshima, Hiroshima, 739-0046, Japan.
Graduate School of Integrated Sciences for Life, Hiroshima University, 1-4-4 Kagamiyama, Higashi-Hiroshima, Hiroshima, 739-8528, Japan.
Virus Genes. 2022 Feb;58(1):70-74. doi: 10.1007/s11262-021-01878-1. Epub 2021 Nov 17.
Endogenous retroviruses (ERVs) are genomic elements derived from retroviral infections in ancestral germ lines. Most ERVs are inactivated by genetic or epigenetic mechanisms, such as DNA methylation. RD-114-virus-related sequence (RDRS) C2a is a feline endogenous retrovirus present in all domestic cats; however, its expression and function are not clearly known. DNA methylation at CpG dinucleotides is a hallmark of silenced ERVs. This study aimed to investigate whether long terminal repeats (LTRs) of RDRS C2a function as a gene regulatory region. The DNA methylation status of RDRS C2a was examined by bisulfite sequencing, and CpG sites in 5' LTR of RDRS C2a were found hypomethylated, whereas those in 3' LTR were hypermethylated in feline cells. Several transcription factor-binding sites were identified in LTRs of RDRS C2a. Luciferase assay suggested that 5' LTR of RDRS C2a exhibited strong transcriptional activity, which was suppressed by in vitro DNA methylation. The study indicates that 5' LTR of RDRS C2a possibly functions as a promoter for itself or neighboring genes.
内源性逆转录病毒（ERVs）是源自祖先生殖系中逆转录病毒感染的基因组元件。大多数 ERVs 通过遗传或表观遗传机制（如 DNA 甲基化）失活。RD-114-病毒相关序列（RDRS）C2a 是一种存在于所有家猫中的猫内源性逆转录病毒；然而，其表达和功能尚不清楚。CpG 二核苷酸处的 DNA 甲基化是沉默 ERVs 的标志。本研究旨在探讨 RDRS C2a 的长末端重复序列（LTR）是否作为基因调控区发挥作用。通过亚硫酸氢盐测序检测 RDRS C2a 的 DNA 甲基化状态，发现 RDRS C2a 的 5' LTR 中的 CpG 位点呈低甲基化，而 3' LTR 中的 CpG 位点呈高甲基化。在 RDRS C2a 的 LTR 中鉴定出几个转录因子结合位点。荧光素酶测定表明，RDRS C2a 的 5' LTR 表现出很强的转录活性，体外 DNA 甲基化可抑制其转录活性。该研究表明，RDRS C2a 的 5' LTR 可能作为自身或邻近基因的启动子发挥作用。
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