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Tri-methylation of histone H3 lysine 4 facilitates gene expression in ageing cells

Transcription of protein coding genes is accompanied by recruitment of COMPASS to promoter-proximal chromatin, which methylates histone H3 lysine 4 (H3K4) to form H3K4me1, H3K4me2 and H3K4me3. Here, we determine the importance of COMPASS in maintaining gene expression across lifespan in budding yeas...

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Autores principales: Cruz, Cristina, Della Rosa, Monica, Krueger, Christel, Gao, Qian, Horkai, Dorottya, King, Michelle, Field, Lucy, Houseley, Jonathan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168286/
https://www.ncbi.nlm.nih.gov/pubmed/30274593
http://dx.doi.org/10.7554/eLife.34081
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author Cruz, Cristina
Della Rosa, Monica
Krueger, Christel
Gao, Qian
Horkai, Dorottya
King, Michelle
Field, Lucy
Houseley, Jonathan
author_facet Cruz, Cristina
Della Rosa, Monica
Krueger, Christel
Gao, Qian
Horkai, Dorottya
King, Michelle
Field, Lucy
Houseley, Jonathan
author_sort Cruz, Cristina
collection PubMed
description Transcription of protein coding genes is accompanied by recruitment of COMPASS to promoter-proximal chromatin, which methylates histone H3 lysine 4 (H3K4) to form H3K4me1, H3K4me2 and H3K4me3. Here, we determine the importance of COMPASS in maintaining gene expression across lifespan in budding yeast. We find that COMPASS mutations reduce replicative lifespan and cause expression defects in almost 500 genes. Although H3K4 methylation is reported to act primarily in gene repression, particularly in yeast, repressive functions are progressively lost with age while hundreds of genes become dependent on H3K4me3 for full expression. Basal and inducible expression of these genes is also impaired in young cells lacking COMPASS components Swd1 or Spp1. Gene induction during ageing is associated with increasing promoter H3K4me3, but H3K4me3 also accumulates in non-promoter regions and the ribosomal DNA. Our results provide clear evidence that H3K4me3 is required to maintain normal expression of many genes across organismal lifespan.
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spelling pubmed-61682862018-10-02 Tri-methylation of histone H3 lysine 4 facilitates gene expression in ageing cells Cruz, Cristina Della Rosa, Monica Krueger, Christel Gao, Qian Horkai, Dorottya King, Michelle Field, Lucy Houseley, Jonathan eLife Chromosomes and Gene Expression Transcription of protein coding genes is accompanied by recruitment of COMPASS to promoter-proximal chromatin, which methylates histone H3 lysine 4 (H3K4) to form H3K4me1, H3K4me2 and H3K4me3. Here, we determine the importance of COMPASS in maintaining gene expression across lifespan in budding yeast. We find that COMPASS mutations reduce replicative lifespan and cause expression defects in almost 500 genes. Although H3K4 methylation is reported to act primarily in gene repression, particularly in yeast, repressive functions are progressively lost with age while hundreds of genes become dependent on H3K4me3 for full expression. Basal and inducible expression of these genes is also impaired in young cells lacking COMPASS components Swd1 or Spp1. Gene induction during ageing is associated with increasing promoter H3K4me3, but H3K4me3 also accumulates in non-promoter regions and the ribosomal DNA. Our results provide clear evidence that H3K4me3 is required to maintain normal expression of many genes across organismal lifespan. eLife Sciences Publications, Ltd 2018-10-02 /pmc/articles/PMC6168286/ /pubmed/30274593 http://dx.doi.org/10.7554/eLife.34081 Text en © 2018, Cruz et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Chromosomes and Gene Expression
Cruz, Cristina
Della Rosa, Monica
Krueger, Christel
Gao, Qian
Horkai, Dorottya
King, Michelle
Field, Lucy
Houseley, Jonathan
Tri-methylation of histone H3 lysine 4 facilitates gene expression in ageing cells
title Tri-methylation of histone H3 lysine 4 facilitates gene expression in ageing cells
title_full Tri-methylation of histone H3 lysine 4 facilitates gene expression in ageing cells
title_fullStr Tri-methylation of histone H3 lysine 4 facilitates gene expression in ageing cells
title_full_unstemmed Tri-methylation of histone H3 lysine 4 facilitates gene expression in ageing cells
title_short Tri-methylation of histone H3 lysine 4 facilitates gene expression in ageing cells
title_sort tri-methylation of histone h3 lysine 4 facilitates gene expression in ageing cells
topic Chromosomes and Gene Expression
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168286/
https://www.ncbi.nlm.nih.gov/pubmed/30274593
http://dx.doi.org/10.7554/eLife.34081
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