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Disordered region of H3K9 methyltransferase Clr4 binds the nucleosome and contributes to its activity

Heterochromatin is a distinctive chromatin structure that is essential for chromosome segregation, genome stability and regulation of gene expression. H3K9 methylation (H3K9me), a hallmark of heterochromatin, is deposited by the Su(var)3-9 family of proteins; however, the mechanism by which H3K9 met...

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Autores principales: Akoury, Elias, Ma, Guoli, Demolin, Segolene, Brönner, Cornelia, Zocco, Manuel, Cirilo, Alexandre, Ivic, Nives, Halic, Mario
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6649693/
https://www.ncbi.nlm.nih.gov/pubmed/31165882
http://dx.doi.org/10.1093/nar/gkz480
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author Akoury, Elias
Ma, Guoli
Demolin, Segolene
Brönner, Cornelia
Zocco, Manuel
Cirilo, Alexandre
Ivic, Nives
Halic, Mario
author_facet Akoury, Elias
Ma, Guoli
Demolin, Segolene
Brönner, Cornelia
Zocco, Manuel
Cirilo, Alexandre
Ivic, Nives
Halic, Mario
author_sort Akoury, Elias
collection PubMed
description Heterochromatin is a distinctive chromatin structure that is essential for chromosome segregation, genome stability and regulation of gene expression. H3K9 methylation (H3K9me), a hallmark of heterochromatin, is deposited by the Su(var)3-9 family of proteins; however, the mechanism by which H3K9 methyltransferases bind and methylate the nucleosome is poorly understood. In this work we determined the interaction of Clr4, the fission yeast H3K9 methyltransferase, with nucleosomes using nuclear magnetic resonance, biochemical and genetic assays. Our study shows that the Clr4 chromodomain binds the H3K9me3 tail and that both, the chromodomain and the disordered region connecting the chromodomain and the SET domain, bind the nucleosome core. We show that interaction of the disordered region with the nucleosome core is independent of H3K9me and contributes to H3K9me in vitro and in vivo. Moreover, we show that those interactions with the nucleosome core are contributing to de novo deposition of H3K9me and to establishment of heterochromatin.
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spelling pubmed-66496932019-07-29 Disordered region of H3K9 methyltransferase Clr4 binds the nucleosome and contributes to its activity Akoury, Elias Ma, Guoli Demolin, Segolene Brönner, Cornelia Zocco, Manuel Cirilo, Alexandre Ivic, Nives Halic, Mario Nucleic Acids Res Gene regulation, Chromatin and Epigenetics Heterochromatin is a distinctive chromatin structure that is essential for chromosome segregation, genome stability and regulation of gene expression. H3K9 methylation (H3K9me), a hallmark of heterochromatin, is deposited by the Su(var)3-9 family of proteins; however, the mechanism by which H3K9 methyltransferases bind and methylate the nucleosome is poorly understood. In this work we determined the interaction of Clr4, the fission yeast H3K9 methyltransferase, with nucleosomes using nuclear magnetic resonance, biochemical and genetic assays. Our study shows that the Clr4 chromodomain binds the H3K9me3 tail and that both, the chromodomain and the disordered region connecting the chromodomain and the SET domain, bind the nucleosome core. We show that interaction of the disordered region with the nucleosome core is independent of H3K9me and contributes to H3K9me in vitro and in vivo. Moreover, we show that those interactions with the nucleosome core are contributing to de novo deposition of H3K9me and to establishment of heterochromatin. Oxford University Press 2019-07-26 2019-06-05 /pmc/articles/PMC6649693/ /pubmed/31165882 http://dx.doi.org/10.1093/nar/gkz480 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
Akoury, Elias
Ma, Guoli
Demolin, Segolene
Brönner, Cornelia
Zocco, Manuel
Cirilo, Alexandre
Ivic, Nives
Halic, Mario
Disordered region of H3K9 methyltransferase Clr4 binds the nucleosome and contributes to its activity
title Disordered region of H3K9 methyltransferase Clr4 binds the nucleosome and contributes to its activity
title_full Disordered region of H3K9 methyltransferase Clr4 binds the nucleosome and contributes to its activity
title_fullStr Disordered region of H3K9 methyltransferase Clr4 binds the nucleosome and contributes to its activity
title_full_unstemmed Disordered region of H3K9 methyltransferase Clr4 binds the nucleosome and contributes to its activity
title_short Disordered region of H3K9 methyltransferase Clr4 binds the nucleosome and contributes to its activity
title_sort disordered region of h3k9 methyltransferase clr4 binds the nucleosome and contributes to its activity
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6649693/
https://www.ncbi.nlm.nih.gov/pubmed/31165882
http://dx.doi.org/10.1093/nar/gkz480
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