Genome Center, MIND Institute, UC Davis, CA, United States.
Genome Center, MIND Institute, UC Davis, CA, United States.
Prog Mol Biol Transl Sci. 2018;157:67-92. doi: 10.1016/bs.pmbts.2017.11.023. Epub 2018 Apr 12.
DNA sequence information alone cannot account for the immense variability between chromosomal alleles within diverse cell types in the brain, whether these differences are observed across time, cell type, or parental origin. The complex control and maintenance of gene expression and modulation are regulated by a multitude of molecular and cellular mechanisms that layer on top of the genetic code. The integration of genetic and environmental signals required for regulating brain development and function is achieved in part by a dynamic epigenetic landscape that includes DNA methylation, histone modifications, and noncoding RNAs. These epigenetic mechanisms establish and maintain core biological processes, including genomic imprinting and entrainment of circadian rhythms. This chapter will focus on how the epigenetic layers of DNA methylation and long, noncoding RNAs interact with circadian rhythms at specific imprinted chromosomal loci associated with the human neurodevelopmental disorders Prader-Willi, Angelman, Kagami-Ogata, and Temple syndromes.
仅 DNA 序列信息无法解释大脑不同细胞类型中染色体等位基因之间的巨大变异性，无论这些差异是在时间、细胞类型还是亲本来源上观察到的。基因表达和调节的复杂控制和维持受到许多分子和细胞机制的调节，这些机制叠加在遗传密码之上。调节大脑发育和功能所需的遗传和环境信号的整合部分是通过一个动态的表观遗传景观来实现的，其中包括 DNA 甲基化、组蛋白修饰和非编码 RNA。这些表观遗传机制建立和维持核心生物过程，包括基因组印记和昼夜节律的驯化。本章将重点讨论 DNA 甲基化和长非编码 RNA 的表观遗传层如何与与人类神经发育障碍普拉德-威利、天使综合征、Kagami-Ogata 和坦普尔综合征相关的特定印迹染色体基因座的昼夜节律相互作用。
