DNA methylation and differentiation: silencing, upregulation and modulation of gene expression.
DNA methylation and differentiation: silencing, upregulation and modulation of gene expression.
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作者：
Ehrlich M;Lacey M
与分化相关的DNA甲基化正受到越来越多的关注，部分原因是新的全基因组分析。这些结果表明，基因体中细胞类型特异性差异甲基化比启动子更频繁。我们回顾了分化过程中DNA甲基化功能的新见解，重点研究了成肌细胞、肌管和骨骼肌与非肌肉样本的甲基化。讨论了亚硫酸盐还原表示测序数据的生物统计学分析。最后，提出了启动子和基因内DNA超甲基化如何影响基因表达的模型，包括提高一些启动子的多梳沉默效率，下调其他启动子而不是沉默它们，对抗异源特异性的增强子，通过抑制CTCF的结合改变染色质构象，通过抑制非编码RNA基因的重叠启动子或通过调节替代mRNA启动子的使用、调节转录终止、调节替代剪接和作为激活染色质扩散的障碍来调节mRNA转录水平。
Differentiation-related DNA methylation is receiving increasing attention, partly owing to new, whole-genome analyses. These revealed that cell type-specific differential methylation in gene bodies is more frequent than in promoters. We review new insights into the functionality of DNA methylation during differentiation, with emphasis on the methylomes of myoblasts, myotubes and skeletal muscle versus non-muscle samples. Biostatistical analyses of data from reduced representation bisulfite sequencing are discussed. Lastly, a model is presented for how promoter and intragenic DNA hypermethylation affect gene expression, including increasing the efficiency of polycomb silencing at some promoters, downmodulating other promoters rather than silencing them, counteracting enhancers with heterologous specificity, altering chromatin conformation by inhibiting the binding of CTCF, modulating mRNA transcript levels by inhibiting overlapping promoters of noncoding RNA genes or by regulating the use of alternative mRNA promoters, modulating transcription termination, regulating alternative splicing and acting as barriers to the spread of activating chromatin.