Cargando…
Substantial Histone Reduction Modulates Genomewide Nucleosomal Occupancy and Global Transcriptional Output
The basic unit of genome packaging is the nucleosome, and nucleosomes have long been proposed to restrict DNA accessibility both to damage and to transcription. Nucleosome number in cells was considered fixed, but recently aging yeast and mammalian cells were shown to contain fewer nucleosomes. We s...
Autores principales: | , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3125158/ https://www.ncbi.nlm.nih.gov/pubmed/21738444 http://dx.doi.org/10.1371/journal.pbio.1001086 |
_version_ | 1782207170016706560 |
---|---|
author | Celona, Barbara Weiner, Assaf Di Felice, Francesca Mancuso, Francesco M. Cesarini, Elisa Rossi, Riccardo L. Gregory, Lorna Baban, Dilair Rossetti, Grazisa Grianti, Paolo Pagani, Massimiliano Bonaldi, Tiziana Ragoussis, Jiannis Friedman, Nir Camilloni, Giorgio Bianchi, Marco E. Agresti, Alessandra |
author_facet | Celona, Barbara Weiner, Assaf Di Felice, Francesca Mancuso, Francesco M. Cesarini, Elisa Rossi, Riccardo L. Gregory, Lorna Baban, Dilair Rossetti, Grazisa Grianti, Paolo Pagani, Massimiliano Bonaldi, Tiziana Ragoussis, Jiannis Friedman, Nir Camilloni, Giorgio Bianchi, Marco E. Agresti, Alessandra |
author_sort | Celona, Barbara |
collection | PubMed |
description | The basic unit of genome packaging is the nucleosome, and nucleosomes have long been proposed to restrict DNA accessibility both to damage and to transcription. Nucleosome number in cells was considered fixed, but recently aging yeast and mammalian cells were shown to contain fewer nucleosomes. We show here that mammalian cells lacking High Mobility Group Box 1 protein (HMGB1) contain a reduced amount of core, linker, and variant histones, and a correspondingly reduced number of nucleosomes, possibly because HMGB1 facilitates nucleosome assembly. Yeast nhp6 mutants lacking Nhp6a and -b proteins, which are related to HMGB1, also have a reduced amount of histones and fewer nucleosomes. Nucleosome limitation in both mammalian and yeast cells increases the sensitivity of DNA to damage, increases transcription globally, and affects the relative expression of about 10% of genes. In yeast nhp6 cells the loss of more than one nucleosome in four does not affect the location of nucleosomes and their spacing, but nucleosomal occupancy. The decrease in nucleosomal occupancy is non-uniform and can be modelled assuming that different nucleosomal sites compete for available histones. Sites with a high propensity to occupation are almost always packaged into nucleosomes both in wild type and nucleosome-depleted cells; nucleosomes on sites with low propensity to occupation are disproportionately lost in nucleosome-depleted cells. We suggest that variation in nucleosome number, by affecting nucleosomal occupancy both genomewide and gene-specifically, constitutes a novel layer of epigenetic regulation. |
format | Online Article Text |
id | pubmed-3125158 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-31251582011-07-07 Substantial Histone Reduction Modulates Genomewide Nucleosomal Occupancy and Global Transcriptional Output Celona, Barbara Weiner, Assaf Di Felice, Francesca Mancuso, Francesco M. Cesarini, Elisa Rossi, Riccardo L. Gregory, Lorna Baban, Dilair Rossetti, Grazisa Grianti, Paolo Pagani, Massimiliano Bonaldi, Tiziana Ragoussis, Jiannis Friedman, Nir Camilloni, Giorgio Bianchi, Marco E. Agresti, Alessandra PLoS Biol Research Article The basic unit of genome packaging is the nucleosome, and nucleosomes have long been proposed to restrict DNA accessibility both to damage and to transcription. Nucleosome number in cells was considered fixed, but recently aging yeast and mammalian cells were shown to contain fewer nucleosomes. We show here that mammalian cells lacking High Mobility Group Box 1 protein (HMGB1) contain a reduced amount of core, linker, and variant histones, and a correspondingly reduced number of nucleosomes, possibly because HMGB1 facilitates nucleosome assembly. Yeast nhp6 mutants lacking Nhp6a and -b proteins, which are related to HMGB1, also have a reduced amount of histones and fewer nucleosomes. Nucleosome limitation in both mammalian and yeast cells increases the sensitivity of DNA to damage, increases transcription globally, and affects the relative expression of about 10% of genes. In yeast nhp6 cells the loss of more than one nucleosome in four does not affect the location of nucleosomes and their spacing, but nucleosomal occupancy. The decrease in nucleosomal occupancy is non-uniform and can be modelled assuming that different nucleosomal sites compete for available histones. Sites with a high propensity to occupation are almost always packaged into nucleosomes both in wild type and nucleosome-depleted cells; nucleosomes on sites with low propensity to occupation are disproportionately lost in nucleosome-depleted cells. We suggest that variation in nucleosome number, by affecting nucleosomal occupancy both genomewide and gene-specifically, constitutes a novel layer of epigenetic regulation. Public Library of Science 2011-06-28 /pmc/articles/PMC3125158/ /pubmed/21738444 http://dx.doi.org/10.1371/journal.pbio.1001086 Text en Celona et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Celona, Barbara Weiner, Assaf Di Felice, Francesca Mancuso, Francesco M. Cesarini, Elisa Rossi, Riccardo L. Gregory, Lorna Baban, Dilair Rossetti, Grazisa Grianti, Paolo Pagani, Massimiliano Bonaldi, Tiziana Ragoussis, Jiannis Friedman, Nir Camilloni, Giorgio Bianchi, Marco E. Agresti, Alessandra Substantial Histone Reduction Modulates Genomewide Nucleosomal Occupancy and Global Transcriptional Output |
title | Substantial Histone Reduction Modulates Genomewide Nucleosomal Occupancy and Global Transcriptional Output |
title_full | Substantial Histone Reduction Modulates Genomewide Nucleosomal Occupancy and Global Transcriptional Output |
title_fullStr | Substantial Histone Reduction Modulates Genomewide Nucleosomal Occupancy and Global Transcriptional Output |
title_full_unstemmed | Substantial Histone Reduction Modulates Genomewide Nucleosomal Occupancy and Global Transcriptional Output |
title_short | Substantial Histone Reduction Modulates Genomewide Nucleosomal Occupancy and Global Transcriptional Output |
title_sort | substantial histone reduction modulates genomewide nucleosomal occupancy and global transcriptional output |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3125158/ https://www.ncbi.nlm.nih.gov/pubmed/21738444 http://dx.doi.org/10.1371/journal.pbio.1001086 |
work_keys_str_mv | AT celonabarbara substantialhistonereductionmodulatesgenomewidenucleosomaloccupancyandglobaltranscriptionaloutput AT weinerassaf substantialhistonereductionmodulatesgenomewidenucleosomaloccupancyandglobaltranscriptionaloutput AT difelicefrancesca substantialhistonereductionmodulatesgenomewidenucleosomaloccupancyandglobaltranscriptionaloutput AT mancusofrancescom substantialhistonereductionmodulatesgenomewidenucleosomaloccupancyandglobaltranscriptionaloutput AT cesarinielisa substantialhistonereductionmodulatesgenomewidenucleosomaloccupancyandglobaltranscriptionaloutput AT rossiriccardol substantialhistonereductionmodulatesgenomewidenucleosomaloccupancyandglobaltranscriptionaloutput AT gregorylorna substantialhistonereductionmodulatesgenomewidenucleosomaloccupancyandglobaltranscriptionaloutput AT babandilair substantialhistonereductionmodulatesgenomewidenucleosomaloccupancyandglobaltranscriptionaloutput AT rossettigrazisa substantialhistonereductionmodulatesgenomewidenucleosomaloccupancyandglobaltranscriptionaloutput AT griantipaolo substantialhistonereductionmodulatesgenomewidenucleosomaloccupancyandglobaltranscriptionaloutput AT paganimassimiliano substantialhistonereductionmodulatesgenomewidenucleosomaloccupancyandglobaltranscriptionaloutput AT bonalditiziana substantialhistonereductionmodulatesgenomewidenucleosomaloccupancyandglobaltranscriptionaloutput AT ragoussisjiannis substantialhistonereductionmodulatesgenomewidenucleosomaloccupancyandglobaltranscriptionaloutput AT friedmannir substantialhistonereductionmodulatesgenomewidenucleosomaloccupancyandglobaltranscriptionaloutput AT camillonigiorgio substantialhistonereductionmodulatesgenomewidenucleosomaloccupancyandglobaltranscriptionaloutput AT bianchimarcoe substantialhistonereductionmodulatesgenomewidenucleosomaloccupancyandglobaltranscriptionaloutput AT agrestialessandra substantialhistonereductionmodulatesgenomewidenucleosomaloccupancyandglobaltranscriptionaloutput |