CpG methylation recruits sequence specific transcription factors essential for tissue specific gene expression.

CpG methylation recruits sequence specific transcription factors essential for tissue specific gene expression.
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DOI:
10.1016/j.bbagrm.2012.02.014
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发表时间:
2012-07
影响因子:
4.7
通讯作者:
Vinson, Charles
Vinson, Charles
中科院分区:
生物学2区
文献类型:
--
作者:
Chatterjee, Raghunath;Vinson, Charles

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CG甲基化是在植物和动物中发现的DNA的表观遗传遗传化学修饰。在哺乳动物中,它对基因表达和正常发育的精确调节至关重要。哺乳动物基因组中的CG二核苷酸被耗尽,这是CG中甲基胞嘧啶化学脱氨基导致TpG的结果。大多数CG二核苷酸是甲基化的,但约15%是未甲基化的。5%的CG聚集成约20,000个区域,称为CG岛(CGI),通常未甲基化。大约一半的CGIs与管家基因有关。相反,基因体、重复序列和转座元件中的CG通常是甲基化的。揭示在正常细胞中运作的表观遗传机制对于理解包括癌症在内的人类疾病中涉及的表观遗传畸变是重要的。随着高通量测序技术的出现,可以鉴定人类基因组中所有3000万个独特CG的CG甲基化状态,并监测分化和发育过程中不同细胞类型的差异。在这里,我们总结了目前对正常细胞中DNA甲基化的理解,并讨论了CG甲基化对组织特异性基因表达的影响。我们还讨论了异常CG甲基化如何导致癌症。
CG methylation is an epigenetically inherited chemical modification of DNA found in plants and animals. In mammals it is essential for accurate regulation of gene expression and normal development. Mammalian genomes are depleted for the CG dinucleotide, a result of the chemical deamination of methyl-cytosine in CG resulting in TpG. Most CG dinucleotides are methylated, but ~ 15% are unmethylated. Five percent of CGs cluster into ~20,000 regions termed CG islands (CGI) which are generally unmethylated. About half of CGIs are associated with housekeeping genes. In contrast, the gene body, repeats and transposable elements in which CGs are generally methylated. Unraveling the epigenetic machinery operating in normal cells is important for understanding the epigenetic aberrations that are involved in human diseases including cancer. With the advent of high-throughput sequencing technologies, it is possible to identify the CG methylation status of all 30 million unique CGs in the human genome, and monitor differences in distinct cell types during differentiation and development. Here we summarize the present understanding of DNA methylation in normal cells and discuss resent observations that CG methylation can have an effect on tissue specific gene expression. We also discuss how aberrant CG methylation can lead to cancer.
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