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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2019
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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. |
format | Online Article Text |
id | pubmed-6546062 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
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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