A human tissue map of 5-hydroxymethylcytosines exhibits tissue specificity through gene and enhancer modulation

Xiao Long Cui; Ji Nie; Jeremy Ku; Urszula Dougherty; Diana C. West-Szymanski; Francois Collin; Christopher K. Ellison; Laura Sieh; Yuhong Ning; Zifeng Deng; Carolyn W.T. Zhao; Anna Bergamaschi; Joel Pekow; Jiangbo Wei; Alana V. Beadell; Zhou Zhang; Geeta Sharma; Raman Talwar; Patrick Arensdorf; Jason Karpus; Ajay Goel; Marc Bissonnette; Wei Zhang; Samuel Levy; Chuan He

doi:10.1038/s41467-020-20001-w

A human tissue map of 5-hydroxymethylcytosines exhibits tissue specificity through gene and enhancer modulation

Xiao Long Cui, Ji Nie, Jeremy Ku, Urszula Dougherty, Diana C. West-Szymanski, Francois Collin, Christopher K. Ellison, Laura Sieh, Yuhong Ning, Zifeng Deng, Carolyn W.T. Zhao, Anna Bergamaschi, Joel Pekow, Jiangbo Wei, Alana V. Beadell, Zhou Zhang, Geeta Sharma, Raman Talwar, Patrick Arensdorf, Jason KarpusAjay Goel, Marc Bissonnette, Wei Zhang, Samuel Levy, Chuan He^*

^*Corresponding author for this work

Preventive Medicine

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

60 Scopus citations

Abstract

DNA 5-hydroxymethylcytosine (5hmC) modification is known to be associated with gene transcription and frequently used as a mark to investigate dynamic DNA methylation conversion during mammalian development and in human diseases. However, the lack of genome-wide 5hmC profiles in different human tissue types impedes drawing generalized conclusions about how 5hmC is implicated in transcription activity and tissue specificity. To meet this need, we describe the development of a 5hmC tissue map by characterizing the genomic distributions of 5hmC in 19 human tissues derived from ten organ systems. Subsequent sequencing results enabled the identification of genome-wide 5hmC distributions that uniquely separates samples by tissue type. Further comparison of the 5hmC profiles with transcriptomes and histone modifications revealed that 5hmC is preferentially enriched on tissue-specific gene bodies and enhancers. Taken together, the results provide an extensive 5hmC map across diverse human tissue types that suggests a potential role of 5hmC in tissue-specific development; as well as a resource to facilitate future studies of DNA demethylation in pathogenesis and the development of 5hmC as biomarkers.

Original language	English (US)
Article number	6161
Journal	Nature communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-20001-w
State	Published - Dec 2020

ASJC Scopus subject areas

Physics and Astronomy(all)
Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41467-020-20001-w

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Cui, X. L., Nie, J., Ku, J., Dougherty, U., West-Szymanski, D. C., Collin, F., Ellison, C. K., Sieh, L., Ning, Y., Deng, Z., Zhao, C. W. T., Bergamaschi, A., Pekow, J., Wei, J., Beadell, A. V., Zhang, Z., Sharma, G., Talwar, R., Arensdorf, P., ... He, C. (2020). A human tissue map of 5-hydroxymethylcytosines exhibits tissue specificity through gene and enhancer modulation. Nature communications, 11(1), Article 6161. https://doi.org/10.1038/s41467-020-20001-w

@article{90b4ec1b43f04cb28849eafb9bf60703,

title = "A human tissue map of 5-hydroxymethylcytosines exhibits tissue specificity through gene and enhancer modulation",

abstract = "DNA 5-hydroxymethylcytosine (5hmC) modification is known to be associated with gene transcription and frequently used as a mark to investigate dynamic DNA methylation conversion during mammalian development and in human diseases. However, the lack of genome-wide 5hmC profiles in different human tissue types impedes drawing generalized conclusions about how 5hmC is implicated in transcription activity and tissue specificity. To meet this need, we describe the development of a 5hmC tissue map by characterizing the genomic distributions of 5hmC in 19 human tissues derived from ten organ systems. Subsequent sequencing results enabled the identification of genome-wide 5hmC distributions that uniquely separates samples by tissue type. Further comparison of the 5hmC profiles with transcriptomes and histone modifications revealed that 5hmC is preferentially enriched on tissue-specific gene bodies and enhancers. Taken together, the results provide an extensive 5hmC map across diverse human tissue types that suggests a potential role of 5hmC in tissue-specific development; as well as a resource to facilitate future studies of DNA demethylation in pathogenesis and the development of 5hmC as biomarkers.",

author = "Cui, {Xiao Long} and Ji Nie and Jeremy Ku and Urszula Dougherty and West-Szymanski, {Diana C.} and Francois Collin and Ellison, {Christopher K.} and Laura Sieh and Yuhong Ning and Zifeng Deng and Zhao, {Carolyn W.T.} and Anna Bergamaschi and Joel Pekow and Jiangbo Wei and Beadell, {Alana V.} and Zhou Zhang and Geeta Sharma and Raman Talwar and Patrick Arensdorf and Jason Karpus and Ajay Goel and Marc Bissonnette and Wei Zhang and Samuel Levy and Chuan He",

note = "Funding Information: We thank Dr. Pieter W. Faber and the staff at the Genomics Facility and Comprehensive Cancer Center sequencing facility at the University of Chicago for performing the NGS sequencing measurements. This work was supported partly by NIH HG006827 (C.H.), R01CA223662 (W.Z.), and U01CA217078 (W.Z. and M.B.). C.H. thanks the Ludwig Center for Metastasis at the University of Chicago and the Chicago Biomedical Consortium Accelerator Award for supports. C.H. is an investigator of the Howard Hughes Medical Institute. Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = dec,

doi = "10.1038/s41467-020-20001-w",

language = "English (US)",

volume = "11",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

Cui, XL, Nie, J, Ku, J, Dougherty, U, West-Szymanski, DC, Collin, F, Ellison, CK, Sieh, L, Ning, Y, Deng, Z, Zhao, CWT, Bergamaschi, A, Pekow, J, Wei, J, Beadell, AV, Zhang, Z, Sharma, G, Talwar, R, Arensdorf, P, Karpus, J, Goel, A, Bissonnette, M, Zhang, W, Levy, S & He, C 2020, 'A human tissue map of 5-hydroxymethylcytosines exhibits tissue specificity through gene and enhancer modulation', Nature communications, vol. 11, no. 1, 6161. https://doi.org/10.1038/s41467-020-20001-w

TY - JOUR

T1 - A human tissue map of 5-hydroxymethylcytosines exhibits tissue specificity through gene and enhancer modulation

AU - Cui, Xiao Long

AU - Nie, Ji

AU - Ku, Jeremy

AU - Dougherty, Urszula

AU - West-Szymanski, Diana C.

AU - Collin, Francois

AU - Ellison, Christopher K.

AU - Sieh, Laura

AU - Ning, Yuhong

AU - Deng, Zifeng

AU - Zhao, Carolyn W.T.

AU - Bergamaschi, Anna

AU - Pekow, Joel

AU - Wei, Jiangbo

AU - Beadell, Alana V.

AU - Zhang, Zhou

AU - Sharma, Geeta

AU - Talwar, Raman

AU - Arensdorf, Patrick

AU - Karpus, Jason

AU - Goel, Ajay

AU - Bissonnette, Marc

AU - Zhang, Wei

AU - Levy, Samuel

AU - He, Chuan

N1 - Funding Information: We thank Dr. Pieter W. Faber and the staff at the Genomics Facility and Comprehensive Cancer Center sequencing facility at the University of Chicago for performing the NGS sequencing measurements. This work was supported partly by NIH HG006827 (C.H.), R01CA223662 (W.Z.), and U01CA217078 (W.Z. and M.B.). C.H. thanks the Ludwig Center for Metastasis at the University of Chicago and the Chicago Biomedical Consortium Accelerator Award for supports. C.H. is an investigator of the Howard Hughes Medical Institute. Publisher Copyright: © 2020, The Author(s).

PY - 2020/12

Y1 - 2020/12

N2 - DNA 5-hydroxymethylcytosine (5hmC) modification is known to be associated with gene transcription and frequently used as a mark to investigate dynamic DNA methylation conversion during mammalian development and in human diseases. However, the lack of genome-wide 5hmC profiles in different human tissue types impedes drawing generalized conclusions about how 5hmC is implicated in transcription activity and tissue specificity. To meet this need, we describe the development of a 5hmC tissue map by characterizing the genomic distributions of 5hmC in 19 human tissues derived from ten organ systems. Subsequent sequencing results enabled the identification of genome-wide 5hmC distributions that uniquely separates samples by tissue type. Further comparison of the 5hmC profiles with transcriptomes and histone modifications revealed that 5hmC is preferentially enriched on tissue-specific gene bodies and enhancers. Taken together, the results provide an extensive 5hmC map across diverse human tissue types that suggests a potential role of 5hmC in tissue-specific development; as well as a resource to facilitate future studies of DNA demethylation in pathogenesis and the development of 5hmC as biomarkers.

AB - DNA 5-hydroxymethylcytosine (5hmC) modification is known to be associated with gene transcription and frequently used as a mark to investigate dynamic DNA methylation conversion during mammalian development and in human diseases. However, the lack of genome-wide 5hmC profiles in different human tissue types impedes drawing generalized conclusions about how 5hmC is implicated in transcription activity and tissue specificity. To meet this need, we describe the development of a 5hmC tissue map by characterizing the genomic distributions of 5hmC in 19 human tissues derived from ten organ systems. Subsequent sequencing results enabled the identification of genome-wide 5hmC distributions that uniquely separates samples by tissue type. Further comparison of the 5hmC profiles with transcriptomes and histone modifications revealed that 5hmC is preferentially enriched on tissue-specific gene bodies and enhancers. Taken together, the results provide an extensive 5hmC map across diverse human tissue types that suggests a potential role of 5hmC in tissue-specific development; as well as a resource to facilitate future studies of DNA demethylation in pathogenesis and the development of 5hmC as biomarkers.

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U2 - 10.1038/s41467-020-20001-w

DO - 10.1038/s41467-020-20001-w

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SN - 2041-1723

VL - 11

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 6161

ER -

A human tissue map of 5-hydroxymethylcytosines exhibits tissue specificity through gene and enhancer modulation

Abstract

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