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Remodeling of epigenome and transcriptome landscapes with aging in mice reveals widespread induction of inflammatory responses

Aging is accompanied by the functional decline of tissues. However, a systematic study of epigenomic and transcriptomic changes across tissues during aging is missing. Here, we generated chromatin maps and transcriptomes from four tissues and one cell type from young, middle-aged, and old mice—yield...

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Autores principales: Benayoun, Bérénice A., Pollina, Elizabeth A., Singh, Param Priya, Mahmoudi, Salah, Harel, Itamar, Casey, Kerriann M., Dulken, Ben W., Kundaje, Anshul, Brunet, Anne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442391/
https://www.ncbi.nlm.nih.gov/pubmed/30858345
http://dx.doi.org/10.1101/gr.240093.118
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author Benayoun, Bérénice A.
Pollina, Elizabeth A.
Singh, Param Priya
Mahmoudi, Salah
Harel, Itamar
Casey, Kerriann M.
Dulken, Ben W.
Kundaje, Anshul
Brunet, Anne
author_facet Benayoun, Bérénice A.
Pollina, Elizabeth A.
Singh, Param Priya
Mahmoudi, Salah
Harel, Itamar
Casey, Kerriann M.
Dulken, Ben W.
Kundaje, Anshul
Brunet, Anne
author_sort Benayoun, Bérénice A.
collection PubMed
description Aging is accompanied by the functional decline of tissues. However, a systematic study of epigenomic and transcriptomic changes across tissues during aging is missing. Here, we generated chromatin maps and transcriptomes from four tissues and one cell type from young, middle-aged, and old mice—yielding 143 high-quality data sets. We focused on chromatin marks linked to gene expression regulation and cell identity: histone H3 trimethylation at lysine 4 (H3K4me3), a mark enriched at promoters, and histone H3 acetylation at lysine 27 (H3K27ac), a mark enriched at active enhancers. Epigenomic and transcriptomic landscapes could easily distinguish between ages, and machine-learning analysis showed that specific epigenomic states could predict transcriptional changes during aging. Analysis of data sets from all tissues identified recurrent age-related chromatin and transcriptional changes in key processes, including the up-regulation of immune system response pathways such as the interferon response. The up-regulation of the interferon response pathway with age was accompanied by increased transcription and chromatin remodeling at specific endogenous retroviral sequences. Pathways misregulated during mouse aging across tissues, notably innate immune pathways, were also misregulated with aging in other vertebrate species—African turquoise killifish, rat, and humans—indicating common signatures of age across species. To date, our data set represents the largest multitissue epigenomic and transcriptomic data set for vertebrate aging. This resource identifies chromatin and transcriptional states that are characteristic of young tissues, which could be leveraged to restore aspects of youthful functionality to old tissues.
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spelling pubmed-64423912019-04-17 Remodeling of epigenome and transcriptome landscapes with aging in mice reveals widespread induction of inflammatory responses Benayoun, Bérénice A. Pollina, Elizabeth A. Singh, Param Priya Mahmoudi, Salah Harel, Itamar Casey, Kerriann M. Dulken, Ben W. Kundaje, Anshul Brunet, Anne Genome Res Resource Aging is accompanied by the functional decline of tissues. However, a systematic study of epigenomic and transcriptomic changes across tissues during aging is missing. Here, we generated chromatin maps and transcriptomes from four tissues and one cell type from young, middle-aged, and old mice—yielding 143 high-quality data sets. We focused on chromatin marks linked to gene expression regulation and cell identity: histone H3 trimethylation at lysine 4 (H3K4me3), a mark enriched at promoters, and histone H3 acetylation at lysine 27 (H3K27ac), a mark enriched at active enhancers. Epigenomic and transcriptomic landscapes could easily distinguish between ages, and machine-learning analysis showed that specific epigenomic states could predict transcriptional changes during aging. Analysis of data sets from all tissues identified recurrent age-related chromatin and transcriptional changes in key processes, including the up-regulation of immune system response pathways such as the interferon response. The up-regulation of the interferon response pathway with age was accompanied by increased transcription and chromatin remodeling at specific endogenous retroviral sequences. Pathways misregulated during mouse aging across tissues, notably innate immune pathways, were also misregulated with aging in other vertebrate species—African turquoise killifish, rat, and humans—indicating common signatures of age across species. To date, our data set represents the largest multitissue epigenomic and transcriptomic data set for vertebrate aging. This resource identifies chromatin and transcriptional states that are characteristic of young tissues, which could be leveraged to restore aspects of youthful functionality to old tissues. Cold Spring Harbor Laboratory Press 2019-04 /pmc/articles/PMC6442391/ /pubmed/30858345 http://dx.doi.org/10.1101/gr.240093.118 Text en © 2019 Benayoun et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Resource
Benayoun, Bérénice A.
Pollina, Elizabeth A.
Singh, Param Priya
Mahmoudi, Salah
Harel, Itamar
Casey, Kerriann M.
Dulken, Ben W.
Kundaje, Anshul
Brunet, Anne
Remodeling of epigenome and transcriptome landscapes with aging in mice reveals widespread induction of inflammatory responses
title Remodeling of epigenome and transcriptome landscapes with aging in mice reveals widespread induction of inflammatory responses
title_full Remodeling of epigenome and transcriptome landscapes with aging in mice reveals widespread induction of inflammatory responses
title_fullStr Remodeling of epigenome and transcriptome landscapes with aging in mice reveals widespread induction of inflammatory responses
title_full_unstemmed Remodeling of epigenome and transcriptome landscapes with aging in mice reveals widespread induction of inflammatory responses
title_short Remodeling of epigenome and transcriptome landscapes with aging in mice reveals widespread induction of inflammatory responses
title_sort remodeling of epigenome and transcriptome landscapes with aging in mice reveals widespread induction of inflammatory responses
topic Resource
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442391/
https://www.ncbi.nlm.nih.gov/pubmed/30858345
http://dx.doi.org/10.1101/gr.240093.118
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