College of Life Sciences, Wuhan University, Hubei Province 430072, PR China.
Biochem Biophys Res Commun. 2010 Jan 22;391(4):1742-7. doi: 10.1016/j.bbrc.2009.12.146. Epub 2009 Dec 31.
Recent studies revealed dramatic changes in circadian clock genes' expression during the perinatal period. In this study, we characterized DNA methylation for three clock genes mPer1, mPer2, and mCry1 at their selected promoter regions during development. Results for the suprachiasmatic nucleus (SCN) and liver (at embryonic day 19, postnatal day 1 and postnatal day 7) were compared to those of sperm. Few methylations were detected for the mPer2 and mCry1 promoters. The 3rd E-box region of the mPer1 promoter exhibited methylation only in sperm. Significant demethylation was observed in the 4th E-box region of the mPer1 promoter between E19 and P1 in the SCN but not in liver tissue. This demethylation state was maintained at P7 for the SCN. Luciferase reporter assays using in vitro methylated promoters revealed an inhibitory effect of promoter methylation on mPer1 expression. The results suggested that epigenetic mechanisms such as DNA methylation might contribute to the developmental expression of clock genes.
最近的研究表明，在围产期，生物钟基因的表达发生了显著变化。在这项研究中，我们在发育过程中对三个生物钟基因 mPer1、mPer2 和 mCry1 的选定启动子区域进行了 DNA 甲基化分析。对比了视交叉上核（SCN）和肝脏（胚胎第 19 天、出生后第 1 天和第 7 天）的结果与精子的结果。mPer2 和 mCry1 启动子的甲基化程度较低。mPer1 启动子的第 3 个 E 盒区域仅在精子中表现出甲基化。在 SCN 中，mPer1 启动子的第 4 个 E 盒区域在 E19 到 P1 之间发生了显著的去甲基化，但在肝脏组织中没有。这种去甲基化状态在 SCN 中一直持续到 P7。使用体外甲基化启动子的荧光素酶报告基因检测显示，启动子甲基化对 mPer1 表达具有抑制作用。研究结果表明，表观遗传机制（如 DNA 甲基化）可能有助于生物钟基因的发育表达。
