期刊
NATURE
卷 523, 期 7559, 页码 212-U189出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature14465
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资金
- National Institutes of Health (NIH) Epigenome Roadmap Project [U01 ES017166]
- National Institute of Neurological Diseases and Stroke grant [R00NS080911]
- Gordon and Betty Moore Foundation [GMBF3034]
- Mary K. Chapman Foundation
- NIH [F32HL110473, K99HL119617]
- Mid-America Transplant Services, St Louis
Understanding the diversity of human tissues is fundamental to disease and requires linking genetic information, which is identical in most of an individual's cells, with epigenetic mechanisms that could have tissue-specific roles. Surveys of DNA methylation in human tissues have established a complex landscape including both tissue-specific and invariant methylation patterns(1,2). Here we report high coverage methylomes that catalogue cytosine methylation in all contexts for the major human organ systems, integrated with matched transcriptomes and genomic sequence. By combining these diverse data types with each individuals' phased genome(3), we identified widespread tissue-specific differential CG methylation (mCG), partially methylated domains, allele-specific methylation and transcription, and the unexpected presence of non-CG methylation (mCH) in almost all human tissues. mCH correlated with tissue-specific functions, and using this mark, we made novel predictions of genes that escape X-chromosome inactivation in specific tissues. Overall, DNA methylation in several genomic contexts varies substantially among human tissues.
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