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A two-state activation mechanism controls the histone methyltransferase Suv39h1

Specialized chromatin domains contribute to nuclear organization and regulation of gene expression. Gene-poor regions are di- and trimethylated at lysine 9 of histone H3 (H3K9me2/3) by the histone methyltransferase, Suv39h1. This enzyme harnesses a positive feedback loop to spread H3K9me2/3 over ext...

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Autores principales: Müller, Manuel M., Fierz, Beat, Bittova, Lenka, Liszczak, Glen, Muir, Tom W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876634/
https://www.ncbi.nlm.nih.gov/pubmed/26807716
http://dx.doi.org/10.1038/nchembio.2008
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author Müller, Manuel M.
Fierz, Beat
Bittova, Lenka
Liszczak, Glen
Muir, Tom W.
author_facet Müller, Manuel M.
Fierz, Beat
Bittova, Lenka
Liszczak, Glen
Muir, Tom W.
author_sort Müller, Manuel M.
collection PubMed
description Specialized chromatin domains contribute to nuclear organization and regulation of gene expression. Gene-poor regions are di- and trimethylated at lysine 9 of histone H3 (H3K9me2/3) by the histone methyltransferase, Suv39h1. This enzyme harnesses a positive feedback loop to spread H3K9me2/3 over extended heterochromatic regions. However, little is known about how feedback loops operate on complex biopolymers such as chromatin, in part because of the difficulty in obtaining suitable substrates. Here we describe the synthesis of multi-domain ‘designer chromatin’ templates and their application to dissecting the regulation of human Suv39h1. We uncovered a two-step activation switch where H3K9me3 recognition and subsequent anchoring of the enzyme to chromatin allosterically promotes methylation activity, and confirmed that this mechanism contributes to chromatin recognition in cells. We propose that this mechanism serves as a paradigm in chromatin biochemistry since it enables highly dynamic sampling of chromatin state combined with targeted modification of desired genomic regions.
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spelling pubmed-48766342016-07-25 A two-state activation mechanism controls the histone methyltransferase Suv39h1 Müller, Manuel M. Fierz, Beat Bittova, Lenka Liszczak, Glen Muir, Tom W. Nat Chem Biol Article Specialized chromatin domains contribute to nuclear organization and regulation of gene expression. Gene-poor regions are di- and trimethylated at lysine 9 of histone H3 (H3K9me2/3) by the histone methyltransferase, Suv39h1. This enzyme harnesses a positive feedback loop to spread H3K9me2/3 over extended heterochromatic regions. However, little is known about how feedback loops operate on complex biopolymers such as chromatin, in part because of the difficulty in obtaining suitable substrates. Here we describe the synthesis of multi-domain ‘designer chromatin’ templates and their application to dissecting the regulation of human Suv39h1. We uncovered a two-step activation switch where H3K9me3 recognition and subsequent anchoring of the enzyme to chromatin allosterically promotes methylation activity, and confirmed that this mechanism contributes to chromatin recognition in cells. We propose that this mechanism serves as a paradigm in chromatin biochemistry since it enables highly dynamic sampling of chromatin state combined with targeted modification of desired genomic regions. 2016-01-25 2016-03 /pmc/articles/PMC4876634/ /pubmed/26807716 http://dx.doi.org/10.1038/nchembio.2008 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Müller, Manuel M.
Fierz, Beat
Bittova, Lenka
Liszczak, Glen
Muir, Tom W.
A two-state activation mechanism controls the histone methyltransferase Suv39h1
title A two-state activation mechanism controls the histone methyltransferase Suv39h1
title_full A two-state activation mechanism controls the histone methyltransferase Suv39h1
title_fullStr A two-state activation mechanism controls the histone methyltransferase Suv39h1
title_full_unstemmed A two-state activation mechanism controls the histone methyltransferase Suv39h1
title_short A two-state activation mechanism controls the histone methyltransferase Suv39h1
title_sort two-state activation mechanism controls the histone methyltransferase suv39h1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876634/
https://www.ncbi.nlm.nih.gov/pubmed/26807716
http://dx.doi.org/10.1038/nchembio.2008
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