DNA methylation-related chromatin remodeling in activity-dependent Bdnf gene regulation
DNA methylation-related chromatin remodeling in activity-dependent Bdnf gene regulation
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DOI：
10.1126/science.1090842
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发表时间：
2003-10-31
期刊：
影响因子：
56.9
通讯作者：
Sun, YE
中科院分区：
文献类型：
--
作者：
Martinowich, K;Hattori, D;Sun, YE
与组蛋白modi结合。阳离子，DNA甲基化通过染色质重塑在基因沉默中起关键作用。DNA甲基化的变化扰乱神经元功能，甲基-CpG结合蛋白MeCP 2的突变与Rett综合征相关。我们报告说，增加合成脑源性神经营养因子（BDNF）在神经元去极化后与减少CpG甲基化的调控区域内的BDNF基因。此外，增加的Bdnf转录涉及MeCP 2-组蛋白脱乙酰酶-mSin 3A阻遏复合物从其启动子的解离。我们的研究结果表明，DNA甲基化相关的染色质重塑是重要的活动依赖性基因调控，可能是神经可塑性的关键。
In conjunction with histone modi. cations, DNA methylation plays critical roles in gene silencing through chromatin remodeling. Changes in DNA methylation perturb neuronal function, and mutations in a methyl-CpG-binding protein, MeCP2, are associated with Rett syndrome. We report that increased synthesis of brain-derived neurotrophic factor (BDNF) in neurons after depolarization correlates with a decrease in CpG methylation within the regulatory region of the Bdnf gene. Moreover, increased Bdnf transcription involves dissociation of the MeCP2-histone deacetylase-mSin3A repression complex from its promoter. Our findings suggest that DNA methylation-related chromatin remodeling is important for activity-dependent gene regulation that may be critical for neural plasticity.