Basic Medicine Laboratory, School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, 516 Jun Gong Road, Shanghai 200093, China.
Steroids. 2010 Dec;75(12):988-97. doi: 10.1016/j.steroids.2010.06.005. Epub 2010 Jun 19.
Thyroid hormones have long been known to play important roles in the development and functions of the central nervous system, however, the precise molecular mechanisms that regulate thyroid hormone-responsive gene expression are not well understood. The present study investigated the role of DNA methylaion and histone acetylation in the effects of perinatal hypothyroidism on regulation of reelin and brain-derived neurotrophic factor (BDNF) gene expression in rat hippocampus. The findings indicated that the activities of DNA methyltransferase (DNMT), methylated reelin and BDNF genes were up-regulated, whereas, the activities of histone acetylases (HAT), the levels of global acetylated histone 3 (H3) and global acetylated histone 4 (H4), and acetylated H3, acetylated H4 at reelin promoter and at BDNF gene promoter for exon II were down-regulated in the hippocampus at the developmental stage of the hypothyroid animals. These results suggest that epigenetic modification of chromatin might underlie the mechanisms of hypothyroidism-induced down-regulation of reelin and BDNF gene expression in developmental rat hippocampus.
甲状腺激素早已被证实对中枢神经系统的发育和功能具有重要作用，然而，调节甲状腺激素反应性基因表达的确切分子机制尚不清楚。本研究探讨了 DNA 甲基化和组蛋白乙酰化在围产期甲状腺功能减退症对调节大鼠海马 reelin 和脑源性神经营养因子（BDNF）基因表达的影响中的作用。研究结果表明，DNA 甲基转移酶（DNMT）、甲基化 reelin 和 BDNF 基因的活性上调，而组蛋白乙酰转移酶（HAT）的活性、组蛋白 H3 和 H4 的整体乙酰化水平，以及 reelin 启动子和 BDNF 基因外显子 II 启动子上的乙酰化 H3 和乙酰化 H4 的水平下调，在甲状腺功能减退动物的发育阶段，海马中出现这种情况。这些结果表明，染色质的表观遗传修饰可能是甲状腺功能减退症引起的发育性大鼠海马 reelin 和 BDNF 基因表达下调的机制。
