Elliott GiNell, Hong Chibo, Xing Xiaoyun, Zhou Xin, Li Daofeng, Coarfa Cristian, Bell Robert J A, Maire Cecile L, Ligon Keith L, Sigaroudinia Mahvash, Gascard Philippe, Tlsty Thea D, Harris R Alan, Schalkwyk Leonard C, Bilenky Misha, Mill Jonathan, Farnham Peggy J, Kellis Manolis, Marra Marco A, Milosavljevic Aleksandar, Hirst Martin, Stormo Gary D, Wang Ting, Costello Joseph F
Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, Missouri 63108, USA.
Brain Tumor Research Center, Department of Neurosurgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California 94115, USA.
Nat Commun. 2015 Feb 18;6:6363. doi: 10.1038/ncomms7363.
The role of intermediate methylation states in DNA is unclear. Here, to comprehensively identify regions of intermediate methylation and their quantitative relationship with gene activity, we apply integrative and comparative epigenomics to 25 human primary cell and tissue samples. We report 18,452 intermediate methylation regions located near 36% of genes and enriched at enhancers, exons and DNase I hypersensitivity sites. Intermediate methylation regions average 57% methylation, are predominantly allele-independent and are conserved across individuals and between mouse and human, suggesting a conserved function. These regions have an intermediate level of active chromatin marks and their associated genes have intermediate transcriptional activity. Exonic intermediate methylation correlates with exon inclusion at a level between that of fully methylated and unmethylated exons, highlighting gene context-dependent functions. We conclude that intermediate DNA methylation is a conserved signature of gene regulation and exon usage.
DNA中间甲基化状态的作用尚不清楚。在此，为了全面鉴定中间甲基化区域及其与基因活性的定量关系，我们对25个人类原代细胞和组织样本应用了整合和比较表观基因组学。我们报告了18452个中间甲基化区域，这些区域位于36%的基因附近，并在增强子、外显子和DNase I超敏位点富集。中间甲基化区域的平均甲基化水平为57%，主要不依赖于等位基因，并且在个体之间以及小鼠和人类之间保守，这表明其具有保守功能。这些区域具有中等水平的活性染色质标记，并且与其相关的基因具有中等转录活性。外显子中间甲基化与外显子包含的相关性处于完全甲基化和未甲基化外显子之间的水平，突出了基因背景依赖性功能。我们得出结论，中间DNA甲基化是基因调控和外显子使用的保守特征。
