Lian Benedict Shi Xiang, Kawasaki Takumi, Kano Norisuke, Ori Daisuke, Ikegawa Moe, Isotani Ayako, Kawai Taro
Laboratory of Molecular Immunobiology, Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology (NAIST), Nara 630-0192, Japan.
Laboratory of Organ Developmental Engineering, Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology (NAIST), Nara 630-0192, Japan.
iScience. 2022 Mar 18;25(4):104118. doi: 10.1016/j.isci.2022.104118. eCollection 2022 Apr 15.
The innate immune system is an immediate defense against infectious pathogens by the production of inflammatory cytokines and other mediators. Deficiencies of epigenetic regulatory enzymes, such as and , cause dysregulation of cytokine expression. However, it is unclear if DNA methylation at a single CpG dinucleotide in a specific gene locus can regulate gene expression. In this study, we demonstrated that CpG+286 and CpG+348 in exon 2 of the gene are similar in various primary mouse cells. In lipopolysaccharide-stimulated condition, hypomethylated CpG+286 promoted expression whereas deletion of CpG+348 led to a reduction in expression associated with enhanced CTCF binding to the locus. Moreover, hypomethylation at CpG+286 in alveolar macrophages from aged mice led to higher expression in response to LPS compared with young mice. Thus, DNA methylation at specific CpG dinucleotides plays an important regulatory role in expression.
先天性免疫系统通过产生炎性细胞因子和其他介质对感染性病原体进行即时防御。表观遗传调控酶（如 和 ）的缺陷会导致细胞因子表达失调。然而，尚不清楚特定基因座中单个CpG二核苷酸处的DNA甲基化是否能调节基因表达。在本研究中，我们证明了 基因外显子2中的CpG+286和CpG+348在各种原代小鼠细胞中是相似的。在脂多糖刺激条件下，低甲基化的CpG+286促进 表达，而删除CpG+348导致 表达降低，这与CTCF与 基因座的结合增强有关。此外，与年轻小鼠相比，老年小鼠肺泡巨噬细胞中CpG+286处的低甲基化导致对脂多糖反应时 表达更高。因此，特定CpG二核苷酸处的DNA甲基化在 表达中起重要的调节作用。
