脑源性神经营养因子(BDNF)的区域表达与发育中的小鼠前脑启动子甲基化的动态模式相关

Kathleen E. Dennis, Pat Levitt
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引用次数: 65

摘要

脑源性神经营养因子(BDNF)在大脑发育和可塑性中起着重要作用。已知BDNF基因表达在发育过程中受到动态调控,但对正常差异表达的调控尚不清楚。基因启动子内CpG二核苷酸的甲基化是一种重要的转录表观遗传控制机制,BDNF复合物启动子中含有多种CpG二核苷酸。我们检测了发育中的小鼠前脑中BDNF的表达,并检查了BDNF启动子中CpG二核苷酸的甲基化是否存在相关模式。数据显示,BDNF在小鼠前脑中动态表达,并且表达与小鼠BDNF启动子eIV中CpG二核苷酸的差异甲基化相关。这些研究表明,该调控区域的DNA甲基化可能是前脑发育过程中控制BDNF差异表达的重要机制。
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Regional expression of brain derived neurotrophic factor (BDNF) is correlated with dynamic patterns of promoter methylation in the developing mouse forebrain

Brain Derived Neurotrophic Factor (BDNF) plays an important role in brain development and plasticity. BDNF gene expression is known to be dynamically regulated during development, but the regulatory controls of normal differential expression are not well understood. Methylation of CpG dinucleotides within gene promoters is emerging as an important epigenetic control mechanism of transcription, and the BDNF complex promoter contains several CpG dinucleotides. We determined BDNF expression in the developing mouse forebrain and examined whether there were correlated patterns of methylation at CpG dinucleotides within the BDNF promoter. The data show that BDNF is dynamically expressed in the mouse forebrain and that expression is correlated with differential methylation specifically at CpG dinucleotides in eIV of the mouse BDNF promoter. These studies demonstrate that DNA methylation of this regulatory region may be an important mechanism controlling differential expression of BDNF during forebrain development.

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