Brudnick Neuropsychiatric Research Institute, Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA 01604, USA.
Neuropsychopharmacology. 2013 Jan;38(1):183-97. doi: 10.1038/npp.2012.78. Epub 2012 May 30.
Many cellular constituents in the human brain permanently exit from the cell cycle during pre- or early postnatal development, but little is known about epigenetic regulation of neuronal and glial epigenomes during maturation and aging, including changes in mood and psychosis spectrum disorders and other cognitive or emotional disease. Here, we summarize the current knowledge base as it pertains to genome organization in the human brain, including the regulation of DNA cytosine methylation and hydroxymethylation, and a subset of (altogether >100) residue-specific histone modifications associated with gene expression, and silencing and various other functional chromatin states. We propose that high-resolution mapping of epigenetic markings in postmortem brain tissue or neural cultures derived from induced pluripotent cells (iPS), in conjunction with transcriptome profiling and whole-genome sequencing, will increasingly be used to define the molecular pathology of specific cases diagnosed with depression, schizophrenia, autism, or other major psychiatric disease. We predict that these highly integrative explorations of genome organization and function will provide an important alternative to conventional approaches in human brain studies, which mainly are aimed at uncovering group effects by diagnosis but generally face limitations because of cohort size.
许多人类大脑中的细胞成分在产前或出生后早期发育过程中永久性地退出细胞周期，但对于神经元和神经胶质表观基因组在成熟和衰老过程中的表观遗传调控知之甚少，包括情绪和精神病谱障碍以及其他认知或情感疾病的变化。在这里，我们总结了当前与人类大脑基因组组织相关的知识库，包括 DNA 胞嘧啶甲基化和羟甲基化的调控，以及与基因表达、沉默和各种其他功能染色质状态相关的（总共>100）残基特异性组蛋白修饰的子集。我们提出，在死后脑组织或诱导多能细胞（iPS）衍生的神经培养物中进行高分辨率的表观遗传标记映射，结合转录组分析和全基因组测序，将越来越多地用于定义被诊断为抑郁症、精神分裂症、自闭症或其他主要精神疾病的特定病例的分子病理学。我们预测，这些对基因组组织和功能的高度综合探索将为人类大脑研究中的传统方法提供一个重要的替代方案，这些传统方法主要旨在通过诊断揭示群体效应，但由于队列规模的限制，通常面临限制。
