Integrative analysis of haplotype-resolved epigenomes across human tissues

Danny Leung; Inkyung Jung; Nisha Rajagopal; Anthony Schmitt; Siddarth Selvaraj; Ah Young Lee; Chia An Yen; Shin Lin; Yiing Lin; Yunjiang Qiu; Wei Xie; Feng Yue; Manoj Hariharan; Pradipta Ray; Samantha Kuan; Lee Edsall; Hongbo Yang; Neil C. Chi; Michael Q. Zhang; Joseph R. Ecker; Bing Ren

doi:10.1038/nature14217

Integrative analysis of haplotype-resolved epigenomes across human tissues

Danny Leung, Inkyung Jung, Nisha Rajagopal, Anthony Schmitt, Siddarth Selvaraj, Ah Young Lee, Chia An Yen, Shin Lin, Yiing Lin, Yunjiang Qiu, Wei Xie, Feng Yue, Manoj Hariharan, Pradipta Ray, Samantha Kuan, Lee Edsall, Hongbo Yang, Neil C. Chi, Michael Q. Zhang, Joseph R. EckerBing Ren^*

^*Corresponding author for this work

Biochemistry and Molecular Genetics

Research output: Contribution to journal › Article › peer-review

168 Scopus citations

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.

Original language	English (US)
Pages (from-to)	350-354
Number of pages	5
Journal	Nature
Volume	518
Issue number	7539
DOIs	https://doi.org/10.1038/nature14217
State	Published - Feb 19 2015

Funding

Acknowledgements This work is supported by the NIH Epigenome Roadmap Project (U01 ES017166), CIRM RN2-00905-1, NIH ES017166, NSFC 91019016, NBRPC 2012CB316503 and NIH Fellowship Grants F32HL110473 and K99HL119617. We thank A. Kulkarni and J. Wu for help with processing RNA-seq data sets, and Y. He and M. Schultz for discussions regarding allelic analyses of RNA-seq data sets. We also thank members of the Ren laboratory for comments.

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Leung, D., Jung, I., Rajagopal, N., Schmitt, A., Selvaraj, S., Lee, A. Y., Yen, C. A., Lin, S., Lin, Y., Qiu, Y., Xie, W., Yue, F., Hariharan, M., Ray, P., Kuan, S., Edsall, L., Yang, H., Chi, N. C., Zhang, M. Q., ... Ren, B. (2015). Integrative analysis of haplotype-resolved epigenomes across human tissues. Nature, 518(7539), 350-354. https://doi.org/10.1038/nature14217

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title = "Integrative analysis of haplotype-resolved epigenomes across human tissues",

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.",

author = "Danny Leung and Inkyung Jung and Nisha Rajagopal and Anthony Schmitt and Siddarth Selvaraj and Lee, {Ah Young} and Yen, {Chia An} and Shin Lin and Yiing Lin and Yunjiang Qiu and Wei Xie and Feng Yue and Manoj Hariharan and Pradipta Ray and Samantha Kuan and Lee Edsall and Hongbo Yang and Chi, {Neil C.} and Zhang, {Michael Q.} and Ecker, {Joseph R.} and Bing Ren",

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AU - Yen, Chia An

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AU - Ecker, Joseph R.

AU - Ren, Bing

N1 - Funding Information: Acknowledgements This work is supported by the NIH Epigenome Roadmap Project (U01 ES017166), CIRM RN2-00905-1, NIH ES017166, NSFC 91019016, NBRPC 2012CB316503 and NIH Fellowship Grants F32HL110473 and K99HL119617. We thank A. Kulkarni and J. Wu for help with processing RNA-seq data sets, and Y. He and M. Schultz for discussions regarding allelic analyses of RNA-seq data sets. We also thank members of the Ren laboratory for comments.

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AB - 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.

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Integrative analysis of haplotype-resolved epigenomes across human tissues

Abstract

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