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Set1-catalyzed H3K4 trimethylation antagonizes the HIR/Asf1/Rtt106 repressor complex to promote histone gene expression and chronological life span

Aging is the main risk factor for many prevalent diseases. However, the molecular mechanisms regulating aging at the cellular level are largely unknown. Using single cell yeast as a model organism, we found that reducing yeast histone proteins accelerates chronological aging and increasing histone s...

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Autores principales: Mei, Qianyun, Xu, Chen, Gogol, Madelaine, Tang, Jie, Chen, Wanping, Yu, Xilan, Workman, Jerry L, Li, Shanshan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468302/
https://www.ncbi.nlm.nih.gov/pubmed/30759223
http://dx.doi.org/10.1093/nar/gkz101
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author Mei, Qianyun
Xu, Chen
Gogol, Madelaine
Tang, Jie
Chen, Wanping
Yu, Xilan
Workman, Jerry L
Li, Shanshan
author_facet Mei, Qianyun
Xu, Chen
Gogol, Madelaine
Tang, Jie
Chen, Wanping
Yu, Xilan
Workman, Jerry L
Li, Shanshan
author_sort Mei, Qianyun
collection PubMed
description Aging is the main risk factor for many prevalent diseases. However, the molecular mechanisms regulating aging at the cellular level are largely unknown. Using single cell yeast as a model organism, we found that reducing yeast histone proteins accelerates chronological aging and increasing histone supply extends chronological life span. We sought to identify pathways that regulate chronological life span by controlling intracellular histone levels. Thus, we screened the histone H3/H4 mutant library to uncover histone residues and posttranslational modifications that regulate histone gene expression. We discovered 15 substitution mutations with reduced histone proteins and 5 mutations with increased histone proteins. Among these mutations, we found Set1 complex-catalyzed H3K4me3 promotes histone gene transcription and maintains normal chronological life span. Unlike the canonical functions of H3K4me3 in gene expression, H3K4me3 facilitates histone gene transcription by acting as a boundary to restrict the spread of the repressive HIR/Asf1/Rtt106 complex from histone gene promoters. Collectively, our study identified a novel mechanism by which H3K4me3 antagonizes the HIR/Asf1/Rtt106 repressor complex to promote histone gene expression and extend chronological life span.
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spelling pubmed-64683022019-04-22 Set1-catalyzed H3K4 trimethylation antagonizes the HIR/Asf1/Rtt106 repressor complex to promote histone gene expression and chronological life span Mei, Qianyun Xu, Chen Gogol, Madelaine Tang, Jie Chen, Wanping Yu, Xilan Workman, Jerry L Li, Shanshan Nucleic Acids Res Gene regulation, Chromatin and Epigenetics Aging is the main risk factor for many prevalent diseases. However, the molecular mechanisms regulating aging at the cellular level are largely unknown. Using single cell yeast as a model organism, we found that reducing yeast histone proteins accelerates chronological aging and increasing histone supply extends chronological life span. We sought to identify pathways that regulate chronological life span by controlling intracellular histone levels. Thus, we screened the histone H3/H4 mutant library to uncover histone residues and posttranslational modifications that regulate histone gene expression. We discovered 15 substitution mutations with reduced histone proteins and 5 mutations with increased histone proteins. Among these mutations, we found Set1 complex-catalyzed H3K4me3 promotes histone gene transcription and maintains normal chronological life span. Unlike the canonical functions of H3K4me3 in gene expression, H3K4me3 facilitates histone gene transcription by acting as a boundary to restrict the spread of the repressive HIR/Asf1/Rtt106 complex from histone gene promoters. Collectively, our study identified a novel mechanism by which H3K4me3 antagonizes the HIR/Asf1/Rtt106 repressor complex to promote histone gene expression and extend chronological life span. Oxford University Press 2019-04-23 2019-02-13 /pmc/articles/PMC6468302/ /pubmed/30759223 http://dx.doi.org/10.1093/nar/gkz101 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Gene regulation, Chromatin and Epigenetics
Mei, Qianyun
Xu, Chen
Gogol, Madelaine
Tang, Jie
Chen, Wanping
Yu, Xilan
Workman, Jerry L
Li, Shanshan
Set1-catalyzed H3K4 trimethylation antagonizes the HIR/Asf1/Rtt106 repressor complex to promote histone gene expression and chronological life span
title Set1-catalyzed H3K4 trimethylation antagonizes the HIR/Asf1/Rtt106 repressor complex to promote histone gene expression and chronological life span
title_full Set1-catalyzed H3K4 trimethylation antagonizes the HIR/Asf1/Rtt106 repressor complex to promote histone gene expression and chronological life span
title_fullStr Set1-catalyzed H3K4 trimethylation antagonizes the HIR/Asf1/Rtt106 repressor complex to promote histone gene expression and chronological life span
title_full_unstemmed Set1-catalyzed H3K4 trimethylation antagonizes the HIR/Asf1/Rtt106 repressor complex to promote histone gene expression and chronological life span
title_short Set1-catalyzed H3K4 trimethylation antagonizes the HIR/Asf1/Rtt106 repressor complex to promote histone gene expression and chronological life span
title_sort set1-catalyzed h3k4 trimethylation antagonizes the hir/asf1/rtt106 repressor complex to promote histone gene expression and chronological life span
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468302/
https://www.ncbi.nlm.nih.gov/pubmed/30759223
http://dx.doi.org/10.1093/nar/gkz101
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