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H3K9me-Independent Gene Silencing in Fission Yeast Heterochromatin by Clr5 and Histone Deacetylases

Nucleosomes in heterochromatic regions bear histone modifications that distinguish them from euchromatic nucleosomes. Among those, histone H3 lysine 9 methylation (H3K9me) and hypoacetylation have been evolutionarily conserved and are found in both multicellular eukaryotes and single-cell model orga...

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Autores principales: Hansen, Klavs R., Hazan, Idit, Shanker, Sreenath, Watt, Stephen, Verhein-Hansen, Janne, Bähler, Jürg, Martienssen, Robert A., Partridge, Janet F., Cohen, Amikam, Thon, Geneviève
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3017117/
https://www.ncbi.nlm.nih.gov/pubmed/21253571
http://dx.doi.org/10.1371/journal.pgen.1001268
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author Hansen, Klavs R.
Hazan, Idit
Shanker, Sreenath
Watt, Stephen
Verhein-Hansen, Janne
Bähler, Jürg
Martienssen, Robert A.
Partridge, Janet F.
Cohen, Amikam
Thon, Geneviève
author_facet Hansen, Klavs R.
Hazan, Idit
Shanker, Sreenath
Watt, Stephen
Verhein-Hansen, Janne
Bähler, Jürg
Martienssen, Robert A.
Partridge, Janet F.
Cohen, Amikam
Thon, Geneviève
author_sort Hansen, Klavs R.
collection PubMed
description Nucleosomes in heterochromatic regions bear histone modifications that distinguish them from euchromatic nucleosomes. Among those, histone H3 lysine 9 methylation (H3K9me) and hypoacetylation have been evolutionarily conserved and are found in both multicellular eukaryotes and single-cell model organisms such as fission yeast. In spite of numerous studies, the relative contributions of the various heterochromatic histone marks to the properties of heterochromatin remain largely undefined. Here, we report that silencing of the fission yeast mating-type cassettes, which are located in a well-characterized heterochromatic region, is hardly affected in cells lacking the H3K9 methyltransferase Clr4. We document the existence of a pathway parallel to H3K9me ensuring gene repression in the absence of Clr4 and identify a silencing factor central to this pathway, Clr5. We find that Clr5 controls gene expression at multiple chromosomal locations in addition to affecting the mating-type region. The histone deacetylase Clr6 acts in the same pathway as Clr5, at least for its effects in the mating-type region, and on a subset of other targets, notably a region recently found to be prone to neo-centromere formation. The genomic targets of Clr5 also include Ste11, a master regulator of sexual differentiation. Hence Clr5, like the multi-functional Atf1 transcription factor which also modulates chromatin structure in the mating-type region, controls sexual differentiation and genome integrity at several levels. Globally, our results point to histone deacetylases as prominent repressors of gene expression in fission yeast heterochromatin. These deacetylases can act in concert with, or independently of, the widely studied H3K9me mark to influence gene silencing at heterochromatic loci.
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spelling pubmed-30171172011-01-20 H3K9me-Independent Gene Silencing in Fission Yeast Heterochromatin by Clr5 and Histone Deacetylases Hansen, Klavs R. Hazan, Idit Shanker, Sreenath Watt, Stephen Verhein-Hansen, Janne Bähler, Jürg Martienssen, Robert A. Partridge, Janet F. Cohen, Amikam Thon, Geneviève PLoS Genet Research Article Nucleosomes in heterochromatic regions bear histone modifications that distinguish them from euchromatic nucleosomes. Among those, histone H3 lysine 9 methylation (H3K9me) and hypoacetylation have been evolutionarily conserved and are found in both multicellular eukaryotes and single-cell model organisms such as fission yeast. In spite of numerous studies, the relative contributions of the various heterochromatic histone marks to the properties of heterochromatin remain largely undefined. Here, we report that silencing of the fission yeast mating-type cassettes, which are located in a well-characterized heterochromatic region, is hardly affected in cells lacking the H3K9 methyltransferase Clr4. We document the existence of a pathway parallel to H3K9me ensuring gene repression in the absence of Clr4 and identify a silencing factor central to this pathway, Clr5. We find that Clr5 controls gene expression at multiple chromosomal locations in addition to affecting the mating-type region. The histone deacetylase Clr6 acts in the same pathway as Clr5, at least for its effects in the mating-type region, and on a subset of other targets, notably a region recently found to be prone to neo-centromere formation. The genomic targets of Clr5 also include Ste11, a master regulator of sexual differentiation. Hence Clr5, like the multi-functional Atf1 transcription factor which also modulates chromatin structure in the mating-type region, controls sexual differentiation and genome integrity at several levels. Globally, our results point to histone deacetylases as prominent repressors of gene expression in fission yeast heterochromatin. These deacetylases can act in concert with, or independently of, the widely studied H3K9me mark to influence gene silencing at heterochromatic loci. Public Library of Science 2011-01-06 /pmc/articles/PMC3017117/ /pubmed/21253571 http://dx.doi.org/10.1371/journal.pgen.1001268 Text en Hansen et al. 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 credited.
spellingShingle Research Article
Hansen, Klavs R.
Hazan, Idit
Shanker, Sreenath
Watt, Stephen
Verhein-Hansen, Janne
Bähler, Jürg
Martienssen, Robert A.
Partridge, Janet F.
Cohen, Amikam
Thon, Geneviève
H3K9me-Independent Gene Silencing in Fission Yeast Heterochromatin by Clr5 and Histone Deacetylases
title H3K9me-Independent Gene Silencing in Fission Yeast Heterochromatin by Clr5 and Histone Deacetylases
title_full H3K9me-Independent Gene Silencing in Fission Yeast Heterochromatin by Clr5 and Histone Deacetylases
title_fullStr H3K9me-Independent Gene Silencing in Fission Yeast Heterochromatin by Clr5 and Histone Deacetylases
title_full_unstemmed H3K9me-Independent Gene Silencing in Fission Yeast Heterochromatin by Clr5 and Histone Deacetylases
title_short H3K9me-Independent Gene Silencing in Fission Yeast Heterochromatin by Clr5 and Histone Deacetylases
title_sort h3k9me-independent gene silencing in fission yeast heterochromatin by clr5 and histone deacetylases
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3017117/
https://www.ncbi.nlm.nih.gov/pubmed/21253571
http://dx.doi.org/10.1371/journal.pgen.1001268
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