The future of neuroepigenetics in the human brain.
The future of neuroepigenetics in the human brain.
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DOI：
10.1016/b978-0-12-800977-2.00008-5
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发表时间：
2014
影响因子：
--
通讯作者：
Akbarian S
中科院分区：
文献类型：
--
作者：
Mitchell A;Roussos P;Peter C;Tsankova N;Akbarian S
复杂的机制将脑细胞的基因组塑造成转录单位、浓缩的染色质簇和许多其他特征，这些特征区分了共享相同遗传物质的各种细胞类型和发育阶段。就在几年前，该领域的重点几乎完全集中在一个单一的标记，CpG甲基化;神经元和神经胶质表观基因组的新兴复杂性现在包括多种类型的DNA胞嘧啶甲基化，100多个残基特异性翻译后组蛋白修饰和组蛋白变体，所有这些都叠加了细胞核内染色体材料的动态和高度调控的三维组织。在这里，我们提供了神经表观遗传学最具创新性的方法及其对人类认知功能和疾病的潜在贡献的更新。我们建议，全面的，细胞类型特异性映射的DNA和组蛋白修饰，染色质相关的RNA，和染色体的“环”和其他三维基因组组织的决定因素将至关重要地推进深入了解疾病的病理生理。例如，将神经元和神经胶质基因组的表观遗传图谱叠加到从阿尔茨海默病到精神分裂症等复杂疾病的遗传图谱上，可以为人类基因组中一些风险相关的非编码序列提供神经功能的重要线索。
Complex mechanisms shape the genome of brain cells into transcriptional units, clusters of condensed chromatin, and many other features that distinguish between various cell types and developmental stages sharing the same genetic material. Only a few years ago, the field’s focus was almost entirely on a single mark, CpG methylation; the emerging complexity of neuronal and glial epigenomes now includes multiple types of DNA cytosine methylation, more than 100 residue-specific posttranslational histone modifications and histone variants, all of which superimposed by a dynamic and highly regulated three-dimensional organization of the chromosomal material inside the cell nucleus. Here, we provide an update on the most innovative approaches in neuroepigenetics and their potential contributions to approach cognitive functions and disorders unique to human. We propose that comprehensive, cell type-specific mappings of DNA and histone modifications, chromatin-associated RNAs, and chromosomal “loopings” and other determinants of three-dimensional genome organization will critically advance insight into the pathophysiology of the disease. For example, superimposing the epigenetic landscapes of neuronal and glial genomes onto genetic maps for complex disorders, ranging from Alzheimer’s disease to schizophrenia, could provide important clues about neurological function for some of the risk-associated noncoding sequences in the human genome.