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PMID: 25693566 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Integrative analysis of haplotype-resolved epigenomes across human tissues.

Nature ·Vol. 518 ·No. 7539 ·2015-02-19 ·Pages 350-354

Leung D, Jung I, Rajagopal N, Schmitt A, Selvaraj S, Lee AY, Yen CA, Lin S, Lin Y, Qiu Y, Xie W, Yue F, Hariharan M, Ray P, Kuan S, Edsall L, Yang H, Chi NC, Zhang MQ, Ecker JR, Ren B

Abstract

Allelic differences between the two homologous chromosomes can affect the propensity of inheritance in humans; however, the extent of such differences in the human genome has yet to be fully explored. Here we delineate allelic chromatin modifications and transcriptomes among a broad set of human tissues, enabled by a chromosome-spanning haplotype reconstruction strategy. The resulting large collection of haplotype-resolved epigenomic maps reveals extensive allelic biases in both chromatin state and transcription, which show considerable variation across tissues and between individuals, and allow us to investigate cis-regulatory relationships between genes and their control sequences. Analyses of histone modification maps also uncover intriguing characteristics of cis-regulatory elements and tissue-restricted activities of repetitive elements. The rich data sets described here will enhance our understanding of the mechanisms by which cis-regulatory elements control gene expression programs.

MeSH Terms
Acetylation Alleles Chromatin/genetics,metabolism Chromosomes, Human/genetics Datasets as Topic Enhancer Elements, Genetic/genetics Epigenesis, Genetic/genetics Epigenomics Genetic Variation/genetics Haplotypes/genetics Histones/metabolism Humans Nucleotide Motifs Organ Specificity/genetics Transcription, Genetic/genetics
Chemicals
Chromatin Histones
Authors & Affiliations
21 authors, click to expand affiliations / ORCID
Leung Danny
Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA.
Jung Inkyung
Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA.
Rajagopal Nisha
Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA.
Schmitt Anthony
Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA.
Selvaraj Siddarth
Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA.
Lee Ah Young
Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA.
Yen Chia-An
Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA.
Lin Shin
Department of Genetics, Stanford University, 300 Pasteur Drive, M-344 Stanford, California 94305, USA. | Department of Cardiovascular Medicine, Stanford University, Falk Building, 870 Quarry Road Stanford, California 94304, USA. | Department of Surgery, Washington University School of Medicine, 660 S. Euclid Ave., Campus Box 8109, St. Louis, Missouri 63110, USA.
Lin Yiing
Department of Genetics, Stanford University, 300 Pasteur Drive, M-344 Stanford, California 94305, USA. | Department of Cardiovascular Medicine, Stanford University, Falk Building, 870 Quarry Road Stanford, California 94304, USA. | Department of Surgery, Washington University School of Medicine, 660 S. Euclid Ave., Campus Box 8109, St. Louis, Missouri 63110, USA.
Qiu Yunjiang
Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA.
Xie Wei
Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA. | Tsinghua University-Peking University Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Yue Feng
Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA. | Biochemistry and Molecular Biology, College of Medicine, The Pennsylvania State University, Hershey, Pennsylvania 17033, USA.
Hariharan Manoj
Genomic Analysis Laboratory, Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA 92093, USA.
Ray Pradipta
Department of Molecular and Cell Biology, Center for Systems Biology, The University of Texas, Dallas. NSERL, RL10, 800 W Campbell Road, Richardson, TX 75080.
Kuan Samantha
Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA.
Edsall Lee
Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA.
Yang Hongbo
Department of Medicine, Division of Cardiology, University of California, San Diego, CA 92093-0613J, USA.
Chi Neil C
Department of Medicine, Division of Cardiology, University of California, San Diego, CA 92093-0613J, USA.
Zhang Michael Q
Department of Molecular and Cell Biology, Center for Systems Biology, The University of Texas, Dallas. NSERL, RL10, 800 W Campbell Road, Richardson, TX 75080. | Bioinformatics Division, Center for Synthetic and Systems Biology, Tsinghua National Laboratory for Information Science and Technology, Tsinghua University, Beijing, China.
Ecker Joseph R
Genomic Analysis Laboratory, Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA 92093, USA. | Department of Cellular and Molecular Medicine, Institute of Genomic Medicine, University of California San Diego, La Jolla, CA 92093, USA.
Ren Bing
Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA. | Department of Medicine, Division of Cardiology, University of California, San Diego, CA 92093-0613J, USA. | UCSD Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA.
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Article Info
Journal
Nature
Abbr.
Nature
ISSN
1476-4687
DOI
10.1038/nature14217
Published
2015-02-19
Pages
350-354
Language
English
Region
England
NLM ID
0410462
PMCID
PMC4449149
Subset
IM
Grants
Howard Hughes Medical Institute · United States
NHLBI NIH HHS · F32HL110473 · United States
NIEHS NIH HHS · U01 ES017166 · United States
NHLBI NIH HHS · R00 HL119617 · United States
NIGMS NIH HHS · T32 GM008666 · United States
NHLBI NIH HHS · F32 HL110473 · United States
NHLBI NIH HHS · K99HL119617 · United States
NHLBI NIH HHS · K99 HL119617 · United States
NIEHS NIH HHS · R01 ES024984 · United States
NIEHS NIH HHS · ES017166 · United States
Databases
GEO
GSE16256, GSE58752
External Links
PubMed source DOI: 10.1038/nature14217 PMC Full Text View journal details
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