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Article: TGF-β signaling alters H4K20me3 status via miR-29 and contributes to cellular senescence and cardiac aging

TitleTGF-β signaling alters H4K20me3 status via miR-29 and contributes to cellular senescence and cardiac aging
Authors
Keywordsadult
animal experiment
cell aging
cell disruption
chromatin immunoprecipitation
Issue Date2018
PublisherNature Research (part of Springer Nature): Fully open access journals. The Journal's web site is located at http://www.nature.com/ncomms/index.html
Citation
Nature Communications, 2018, v. 9 n. 1, p. article no. 2560 How to Cite?
AbstractCellular senescence is a well-orchestrated programmed process involved in age-related pathologies, tumor suppression and embryonic development. TGF-β/Smad is one of the predominant pathways that regulate damage-induced and developmentally programmed senescence. Here we show that canonical TGF-β signaling promotes senescence via miR-29-induced loss of H4K20me3. Mechanistically, oxidative stress triggers TGF-β signaling. Activated TGF-β signaling gives rise to acute accumulation of miR-29a and miR-29c, both of which directly suppress their novel target, Suv4-20h, thus reducing H4K20me3 abundance in a Smad-dependent manner, which compromises DNA damage repair and genome maintenance. Loss of H4K20me3 mediated by the senescent TGF-β/miR-29 pathway contributes to cardiac aging in vivo. Disruption of TGF-β signaling restores H4K20me3 and improves cardiac function in aged mice. Our study highlights the sequential mechanisms underlying the regulation of senescence, from senescence-inducing triggers to activation of responsive signaling followed by specific epigenetic alterations, shedding light on potential therapeutic interventions in cardiac aging.
Persistent Identifierhttp://hdl.handle.net/10722/277181
ISSN
2017 Impact Factor: 12.353
2015 SCImago Journal Rankings: 6.539
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorLyu, G-
dc.contributor.authorGuan, Y-
dc.contributor.authorZhang, C-
dc.contributor.authorZong, L-
dc.contributor.authorSun, L-
dc.contributor.authorHuang, X-
dc.contributor.authorHuang, L-
dc.contributor.authorZhang, L-
dc.contributor.authorTian, XL-
dc.contributor.authorZhou, Z-
dc.contributor.authorTao, W-
dc.date.accessioned2019-09-20T08:46:09Z-
dc.date.available2019-09-20T08:46:09Z-
dc.date.issued2018-
dc.identifier.citationNature Communications, 2018, v. 9 n. 1, p. article no. 2560-
dc.identifier.issn2041-1723-
dc.identifier.urihttp://hdl.handle.net/10722/277181-
dc.description.abstractCellular senescence is a well-orchestrated programmed process involved in age-related pathologies, tumor suppression and embryonic development. TGF-β/Smad is one of the predominant pathways that regulate damage-induced and developmentally programmed senescence. Here we show that canonical TGF-β signaling promotes senescence via miR-29-induced loss of H4K20me3. Mechanistically, oxidative stress triggers TGF-β signaling. Activated TGF-β signaling gives rise to acute accumulation of miR-29a and miR-29c, both of which directly suppress their novel target, Suv4-20h, thus reducing H4K20me3 abundance in a Smad-dependent manner, which compromises DNA damage repair and genome maintenance. Loss of H4K20me3 mediated by the senescent TGF-β/miR-29 pathway contributes to cardiac aging in vivo. Disruption of TGF-β signaling restores H4K20me3 and improves cardiac function in aged mice. Our study highlights the sequential mechanisms underlying the regulation of senescence, from senescence-inducing triggers to activation of responsive signaling followed by specific epigenetic alterations, shedding light on potential therapeutic interventions in cardiac aging.-
dc.languageeng-
dc.publisherNature Research (part of Springer Nature): Fully open access journals. The Journal's web site is located at http://www.nature.com/ncomms/index.html-
dc.relation.ispartofNature Communications-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectadult-
dc.subjectanimal experiment-
dc.subjectcell aging-
dc.subjectcell disruption-
dc.subjectchromatin immunoprecipitation-
dc.titleTGF-β signaling alters H4K20me3 status via miR-29 and contributes to cellular senescence and cardiac aging-
dc.typeArticle-
dc.identifier.emailZhou, Z: zhongjun@hku.hk-
dc.identifier.authorityZhou, Z=rp00503-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s41467-018-04994-z-
dc.identifier.pmid29967491-
dc.identifier.pmcidPMC6028646-
dc.identifier.scopuseid_2-s2.0-85049396675-
dc.identifier.hkuros305499-
dc.identifier.volume9-
dc.identifier.issue1-
dc.identifier.spagearticle no. 2560-
dc.identifier.epagearticle no. 2560-
dc.publisher.placeUnited Kingdom-

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