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Integrative Epigenome Map of the Normal Human Prostate Provides Insights Into Prostate Cancer Predisposition
Cells of all tissues in the human body share almost the exact same DNA sequence, but the epigenomic landscape can be drastically distinct. To improve our understanding of the epigenetic abnormalities in prostate-related diseases, it is important to use the epigenome of normal prostate as a reference...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427514/ https://www.ncbi.nlm.nih.gov/pubmed/34513844 http://dx.doi.org/10.3389/fcell.2021.723676 |
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author | Wang, Tao Song, Juan Qu, Min Gao, Xu Zhang, Wenhui Wang, Ziwei Zhao, Lin Wang, Yan Li, Bing Li, Jing Yang, Jinjian |
author_facet | Wang, Tao Song, Juan Qu, Min Gao, Xu Zhang, Wenhui Wang, Ziwei Zhao, Lin Wang, Yan Li, Bing Li, Jing Yang, Jinjian |
author_sort | Wang, Tao |
collection | PubMed |
description | Cells of all tissues in the human body share almost the exact same DNA sequence, but the epigenomic landscape can be drastically distinct. To improve our understanding of the epigenetic abnormalities in prostate-related diseases, it is important to use the epigenome of normal prostate as a reference. Although previous efforts have provided critical insights into the genetic and transcriptomic features of the normal prostate, a comprehensive epigenome map has been lacking. To address this need, we conducted a Roadmap Epigenomics legacy project integrating six histone marks (H3K4me1, H3K4me3, H3K9me3, H3K36me3, H3K27me3, and H3K27ac) with complete DNA methylome, transcriptome, and chromatin accessibility data to produce a comprehensive epigenome map of normal prostate tissue. Our epigenome map is composed of 18 chromatin states each with unique signatures of DNA methylation, chromatin accessibility, and gene expression. This map provides a high-resolution comprehensive annotation of regulatory regions of the prostate, including 105,593 enhancer and 70,481 promoter elements, which account for 5.3% of the genome. By comparing with other epigenomes, we identified 7,580 prostate-specific active enhancers associated with prostate development. Epigenomic annotation of GWAS SNPs associated with prostate cancers revealed that two out of nine SNPs within prostate enhancer regions destroyed putative androgen receptor (AR) binding motif. A notable SNP rs17694493, might decouple AR’s repressive effect on CDKN2B-AS1 and cell cycle regulation, thereby playing a causal role in predisposing cancer risk. The comprehensive epigenome map of the prostate is valuable for investigating prostate-related diseases. |
format | Online Article Text |
id | pubmed-8427514 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84275142021-09-10 Integrative Epigenome Map of the Normal Human Prostate Provides Insights Into Prostate Cancer Predisposition Wang, Tao Song, Juan Qu, Min Gao, Xu Zhang, Wenhui Wang, Ziwei Zhao, Lin Wang, Yan Li, Bing Li, Jing Yang, Jinjian Front Cell Dev Biol Cell and Developmental Biology Cells of all tissues in the human body share almost the exact same DNA sequence, but the epigenomic landscape can be drastically distinct. To improve our understanding of the epigenetic abnormalities in prostate-related diseases, it is important to use the epigenome of normal prostate as a reference. Although previous efforts have provided critical insights into the genetic and transcriptomic features of the normal prostate, a comprehensive epigenome map has been lacking. To address this need, we conducted a Roadmap Epigenomics legacy project integrating six histone marks (H3K4me1, H3K4me3, H3K9me3, H3K36me3, H3K27me3, and H3K27ac) with complete DNA methylome, transcriptome, and chromatin accessibility data to produce a comprehensive epigenome map of normal prostate tissue. Our epigenome map is composed of 18 chromatin states each with unique signatures of DNA methylation, chromatin accessibility, and gene expression. This map provides a high-resolution comprehensive annotation of regulatory regions of the prostate, including 105,593 enhancer and 70,481 promoter elements, which account for 5.3% of the genome. By comparing with other epigenomes, we identified 7,580 prostate-specific active enhancers associated with prostate development. Epigenomic annotation of GWAS SNPs associated with prostate cancers revealed that two out of nine SNPs within prostate enhancer regions destroyed putative androgen receptor (AR) binding motif. A notable SNP rs17694493, might decouple AR’s repressive effect on CDKN2B-AS1 and cell cycle regulation, thereby playing a causal role in predisposing cancer risk. The comprehensive epigenome map of the prostate is valuable for investigating prostate-related diseases. Frontiers Media S.A. 2021-08-26 /pmc/articles/PMC8427514/ /pubmed/34513844 http://dx.doi.org/10.3389/fcell.2021.723676 Text en Copyright © 2021 Wang, Song, Qu, Gao, Zhang, Wang, Zhao, Wang, Li, Li and Yang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Wang, Tao Song, Juan Qu, Min Gao, Xu Zhang, Wenhui Wang, Ziwei Zhao, Lin Wang, Yan Li, Bing Li, Jing Yang, Jinjian Integrative Epigenome Map of the Normal Human Prostate Provides Insights Into Prostate Cancer Predisposition |
title | Integrative Epigenome Map of the Normal Human Prostate Provides Insights Into Prostate Cancer Predisposition |
title_full | Integrative Epigenome Map of the Normal Human Prostate Provides Insights Into Prostate Cancer Predisposition |
title_fullStr | Integrative Epigenome Map of the Normal Human Prostate Provides Insights Into Prostate Cancer Predisposition |
title_full_unstemmed | Integrative Epigenome Map of the Normal Human Prostate Provides Insights Into Prostate Cancer Predisposition |
title_short | Integrative Epigenome Map of the Normal Human Prostate Provides Insights Into Prostate Cancer Predisposition |
title_sort | integrative epigenome map of the normal human prostate provides insights into prostate cancer predisposition |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427514/ https://www.ncbi.nlm.nih.gov/pubmed/34513844 http://dx.doi.org/10.3389/fcell.2021.723676 |
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