title: Human body epigenome maps reveal noncanonical DNA methylation variation.
abstract: 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. 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, 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.
authors.affiliation: 1] Bioinformatics Program, University of California, San Diego, La Jolla, California 92093, USA [2] Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Schultz
authors.affiliation: 1] Bioinformatics Program, University of California, San Diego, La Jolla, California 92093, USA [2] Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: Yupeng
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Whitaker
authors.affiliation: Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: Manoj
authors.initials: M
authors.lastname: Hariharan
authors.affiliation: 1] Computational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA [2] Department of Cognitive Science, University of California, San Diego, La Jolla, California 92037, USA.
authors.forename: Eran A
authors.initials: EA
authors.lastname: Mukamel
authors.affiliation: Ludwig Institute for Cancer Research, La Jolla, California 92093, USA.
authors.forename: Danny
authors.initials: D
authors.lastname: Leung
authors.affiliation: Ludwig Institute for Cancer Research, La Jolla, California 92093, USA.
authors.forename: Nisha
authors.initials: N
authors.lastname: Rajagopal
authors.affiliation: Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Nery
authors.affiliation: Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Urich
authors.affiliation: Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: Huaming
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Genetics, Stanford University, 300 Pasteur Drive, M-344 Stanford, California 94305, USA.
authors.forename: Shin
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Surgery, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8109, St Louis, Missouri 63110, USA.
authors.forename: Yiing
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Ludwig Institute for Cancer Research, La Jolla, California 92093, USA.
authors.forename: Inkyung
authors.initials: I
authors.lastname: Jung
authors.affiliation: Ludwig Institute for Cancer Research, La Jolla, California 92093, USA.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Schmitt
authors.affiliation: Bioinformatics Program, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Siddarth
authors.initials: S
authors.lastname: Selvaraj
authors.affiliation: 1] Ludwig Institute for Cancer Research, La Jolla, California 92093, USA [2] University of California, San Diego School of Medicine, Department of Cellular and Molecular Medicine, Institute of Genomic Medicine, La Jolla, California 92093, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Ren
authors.affiliation: 1] Computational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA [2] Division of Biological Sciences, University of California at San Diego, La Jolla, California 92037, USA [3] Howard Hughes Medical Institute, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Terrence J
authors.initials: TJ
authors.lastname: Sejnowski
authors.affiliation: 1] Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093, USA [2] Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: 1] Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA [2] Howard Hughes Medical Institute, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Ecker
mesh_terms: D000367:Age Factors; D000483:Alleles; D002874:Chromosome Mapping; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D014644:Genetic Variation; D006801:Humans; D008297:Male; D009928:Organ Specificity