Region-specific H3K9me3 gain in aged somatic tissues in Caenorhabditis elegans.

Epigenetic alterations occur as organisms age, and lead to chromatin deterioration, loss of transcriptional silencing and genomic instability. Dysregulation of the epigenome has been associated with increased susceptibility to age-related disorders. In this study, we aimed to characterize the age-de...

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Autores principales:	Cheng-Lin Li, Mintie Pu, Wenke Wang, Amaresh Chaturbedi, Felicity J Emerson, Siu Sylvia Lee
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/5c6e46d57f524de1be5e789ef7bbb211
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spelling	oai:doaj.org-article:5c6e46d57f524de1be5e789ef7bbb2112021-12-02T20:03:03ZRegion-specific H3K9me3 gain in aged somatic tissues in Caenorhabditis elegans.1553-73901553-740410.1371/journal.pgen.1009432https://doaj.org/article/5c6e46d57f524de1be5e789ef7bbb2112021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.pgen.1009432https://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Epigenetic alterations occur as organisms age, and lead to chromatin deterioration, loss of transcriptional silencing and genomic instability. Dysregulation of the epigenome has been associated with increased susceptibility to age-related disorders. In this study, we aimed to characterize the age-dependent changes of the epigenome and, in turn, to understand epigenetic processes that drive aging phenotypes. We focused on the aging-associated changes in the repressive histone marks H3K9me3 and H3K27me3 in C. elegans. We observed region-specific gain and loss of both histone marks, but the changes are more evident for H3K9me3. We further found alteration of heterochromatic boundaries in aged somatic tissues. Interestingly, we discovered that the most statistically significant changes reflected H3K9me3-marked regions that are formed during aging, and are absent in developing worms, which we termed "aging-specific repressive regions" (ASRRs). These ASRRs preferentially occur in genic regions that are marked by high levels of H3K9me2 and H3K36me2 in larval stages. Maintenance of high H3K9me2 levels in these regions have been shown to correlate with a longer lifespan. Next, we examined whether the changes in repressive histone marks lead to de-silencing of repetitive DNA elements, as reported for several other organisms. We observed increased expression of active repetitive DNA elements but not global re-activation of silent repeats in old worms, likely due to the distributed nature of repetitive elements in the C. elegans genome. Intriguingly, CELE45, a putative short interspersed nuclear element (SINE), was greatly overexpressed at old age and upon heat stress. SINEs have been suggested to regulate transcription in response to various cellular stresses in mammals. It is likely that CELE45 RNAs also play roles in stress response and aging in C. elegans. Taken together, our study revealed significant and specific age-dependent changes in repressive histone modifications and repetitive elements, providing important insights into aging biology.Cheng-Lin LiMintie PuWenke WangAmaresh ChaturbediFelicity J EmersonSiu Sylvia LeePublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 17, Iss 9, p e1009432 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Cheng-Lin Li Mintie Pu Wenke Wang Amaresh Chaturbedi Felicity J Emerson Siu Sylvia Lee Region-specific H3K9me3 gain in aged somatic tissues in Caenorhabditis elegans.
description	Epigenetic alterations occur as organisms age, and lead to chromatin deterioration, loss of transcriptional silencing and genomic instability. Dysregulation of the epigenome has been associated with increased susceptibility to age-related disorders. In this study, we aimed to characterize the age-dependent changes of the epigenome and, in turn, to understand epigenetic processes that drive aging phenotypes. We focused on the aging-associated changes in the repressive histone marks H3K9me3 and H3K27me3 in C. elegans. We observed region-specific gain and loss of both histone marks, but the changes are more evident for H3K9me3. We further found alteration of heterochromatic boundaries in aged somatic tissues. Interestingly, we discovered that the most statistically significant changes reflected H3K9me3-marked regions that are formed during aging, and are absent in developing worms, which we termed "aging-specific repressive regions" (ASRRs). These ASRRs preferentially occur in genic regions that are marked by high levels of H3K9me2 and H3K36me2 in larval stages. Maintenance of high H3K9me2 levels in these regions have been shown to correlate with a longer lifespan. Next, we examined whether the changes in repressive histone marks lead to de-silencing of repetitive DNA elements, as reported for several other organisms. We observed increased expression of active repetitive DNA elements but not global re-activation of silent repeats in old worms, likely due to the distributed nature of repetitive elements in the C. elegans genome. Intriguingly, CELE45, a putative short interspersed nuclear element (SINE), was greatly overexpressed at old age and upon heat stress. SINEs have been suggested to regulate transcription in response to various cellular stresses in mammals. It is likely that CELE45 RNAs also play roles in stress response and aging in C. elegans. Taken together, our study revealed significant and specific age-dependent changes in repressive histone modifications and repetitive elements, providing important insights into aging biology.
format	article
author	Cheng-Lin Li Mintie Pu Wenke Wang Amaresh Chaturbedi Felicity J Emerson Siu Sylvia Lee
author_facet	Cheng-Lin Li Mintie Pu Wenke Wang Amaresh Chaturbedi Felicity J Emerson Siu Sylvia Lee
author_sort	Cheng-Lin Li
title	Region-specific H3K9me3 gain in aged somatic tissues in Caenorhabditis elegans.
title_short	Region-specific H3K9me3 gain in aged somatic tissues in Caenorhabditis elegans.
title_full	Region-specific H3K9me3 gain in aged somatic tissues in Caenorhabditis elegans.
title_fullStr	Region-specific H3K9me3 gain in aged somatic tissues in Caenorhabditis elegans.
title_full_unstemmed	Region-specific H3K9me3 gain in aged somatic tissues in Caenorhabditis elegans.
title_sort	region-specific h3k9me3 gain in aged somatic tissues in caenorhabditis elegans.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/5c6e46d57f524de1be5e789ef7bbb211
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Region-specific H3K9me3 gain in aged somatic tissues in Caenorhabditis elegans.

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