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Structural basis of recognition and destabilization of the histone H2B ubiquitinated nucleosome by the DOT1L histone H3 Lys79 methyltransferase

DOT1L is a histone H3 Lys79 methyltransferase whose activity is stimulated by histone H2B Lys120 ubiquitination, suggesting cross-talk between histone H3 methylation and H2B ubiquitination. Here, we present cryo-EM structures of DOT1L complexes with unmodified or H2B ubiquitinated nucleosomes, showi...

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Autores principales: Jang, Seongmin, Kang, Chanshin, Yang, Han-Sol, Jung, Taeyang, Hebert, Hans, Chung, Ka Young, Kim, Seung Joong, Hohng, Sungchul, Song, Ji-Joon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546062/
https://www.ncbi.nlm.nih.gov/pubmed/30923167
http://dx.doi.org/10.1101/gad.323790.118
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author Jang, Seongmin
Kang, Chanshin
Yang, Han-Sol
Jung, Taeyang
Hebert, Hans
Chung, Ka Young
Kim, Seung Joong
Hohng, Sungchul
Song, Ji-Joon
author_facet Jang, Seongmin
Kang, Chanshin
Yang, Han-Sol
Jung, Taeyang
Hebert, Hans
Chung, Ka Young
Kim, Seung Joong
Hohng, Sungchul
Song, Ji-Joon
author_sort Jang, Seongmin
collection PubMed
description DOT1L is a histone H3 Lys79 methyltransferase whose activity is stimulated by histone H2B Lys120 ubiquitination, suggesting cross-talk between histone H3 methylation and H2B ubiquitination. Here, we present cryo-EM structures of DOT1L complexes with unmodified or H2B ubiquitinated nucleosomes, showing that DOT1L recognizes H2B ubiquitin and the H2A/H2B acidic patch through a C-terminal hydrophobic helix and an arginine anchor in DOT1L, respectively. Furthermore, the structures combined with single-molecule FRET experiments show that H2B ubiquitination enhances a noncatalytic function of the DOT1L-destabilizing nucleosome. These results establish the molecular basis of the cross-talk between H2B ubiquitination and H3 Lys79 methylation as well as nucleosome destabilization by DOT1L.
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spelling pubmed-65460622019-12-01 Structural basis of recognition and destabilization of the histone H2B ubiquitinated nucleosome by the DOT1L histone H3 Lys79 methyltransferase Jang, Seongmin Kang, Chanshin Yang, Han-Sol Jung, Taeyang Hebert, Hans Chung, Ka Young Kim, Seung Joong Hohng, Sungchul Song, Ji-Joon Genes Dev Research Communication DOT1L is a histone H3 Lys79 methyltransferase whose activity is stimulated by histone H2B Lys120 ubiquitination, suggesting cross-talk between histone H3 methylation and H2B ubiquitination. Here, we present cryo-EM structures of DOT1L complexes with unmodified or H2B ubiquitinated nucleosomes, showing that DOT1L recognizes H2B ubiquitin and the H2A/H2B acidic patch through a C-terminal hydrophobic helix and an arginine anchor in DOT1L, respectively. Furthermore, the structures combined with single-molecule FRET experiments show that H2B ubiquitination enhances a noncatalytic function of the DOT1L-destabilizing nucleosome. These results establish the molecular basis of the cross-talk between H2B ubiquitination and H3 Lys79 methylation as well as nucleosome destabilization by DOT1L. Cold Spring Harbor Laboratory Press 2019-06-01 /pmc/articles/PMC6546062/ /pubmed/30923167 http://dx.doi.org/10.1101/gad.323790.118 Text en © 2019 Jang et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research Communication
Jang, Seongmin
Kang, Chanshin
Yang, Han-Sol
Jung, Taeyang
Hebert, Hans
Chung, Ka Young
Kim, Seung Joong
Hohng, Sungchul
Song, Ji-Joon
Structural basis of recognition and destabilization of the histone H2B ubiquitinated nucleosome by the DOT1L histone H3 Lys79 methyltransferase
title Structural basis of recognition and destabilization of the histone H2B ubiquitinated nucleosome by the DOT1L histone H3 Lys79 methyltransferase
title_full Structural basis of recognition and destabilization of the histone H2B ubiquitinated nucleosome by the DOT1L histone H3 Lys79 methyltransferase
title_fullStr Structural basis of recognition and destabilization of the histone H2B ubiquitinated nucleosome by the DOT1L histone H3 Lys79 methyltransferase
title_full_unstemmed Structural basis of recognition and destabilization of the histone H2B ubiquitinated nucleosome by the DOT1L histone H3 Lys79 methyltransferase
title_short Structural basis of recognition and destabilization of the histone H2B ubiquitinated nucleosome by the DOT1L histone H3 Lys79 methyltransferase
title_sort structural basis of recognition and destabilization of the histone h2b ubiquitinated nucleosome by the dot1l histone h3 lys79 methyltransferase
topic Research Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546062/
https://www.ncbi.nlm.nih.gov/pubmed/30923167
http://dx.doi.org/10.1101/gad.323790.118
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