Dennis Kathleen E, Levitt Pat
Vanderbilt Kennedy Center for Research on Human Development and Department of Pharmacology, Vanderbilt University School of Medicine, 465 21st Avenue S. MRBIII, Rm 8114, Nashville, TN 37232, USA.
Brain Res Mol Brain Res. 2005 Oct 31;140(1-2):1-9. doi: 10.1016/j.molbrainres.2005.06.014. Epub 2005 Jul 28.
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.
脑源性神经营养因子(BDNF)在大脑发育和可塑性方面发挥着重要作用。已知BDNF基因表达在发育过程中受到动态调控,但正常差异表达的调控机制尚未完全明确。基因启动子内CpG二核苷酸的甲基化正成为一种重要的转录表观遗传调控机制,而BDNF复合启动子包含多个CpG二核苷酸。我们测定了发育中小鼠前脑内BDNF的表达,并检测了BDNF启动子内CpG二核苷酸处是否存在相关的甲基化模式。数据表明,BDNF在小鼠前脑中动态表达,且该表达与小鼠BDNF启动子eIV中CpG二核苷酸处的差异甲基化相关。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。