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Histone H3K23-specific acetylation by MORF is coupled to H3K14 acylation
Acetylation of histone H3K23 has emerged as an essential posttranslational modification associated with cancer and learning and memory impairment, yet our understanding of this epigenetic mark remains insufficient. Here, we identify the native MORF complex as a histone H3K23-specific acetyltransfera...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797804/ https://www.ncbi.nlm.nih.gov/pubmed/31624313 http://dx.doi.org/10.1038/s41467-019-12551-5 |
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author | Klein, Brianna J. Jang, Suk Min Lachance, Catherine Mi, Wenyi Lyu, Jie Sakuraba, Shun Krajewski, Krzysztof Wang, Wesley W. Sidoli, Simone Liu, Jiuyang Zhang, Yi Wang, Xiaolu Warfield, Becka M. Kueh, Andrew J. Voss, Anne K. Thomas, Tim Garcia, Benjamin A. Liu, Wenshe R. Strahl, Brian D. Kono, Hidetoshi Li, Wei Shi, Xiaobing Côté, Jacques Kutateladze, Tatiana G. |
author_facet | Klein, Brianna J. Jang, Suk Min Lachance, Catherine Mi, Wenyi Lyu, Jie Sakuraba, Shun Krajewski, Krzysztof Wang, Wesley W. Sidoli, Simone Liu, Jiuyang Zhang, Yi Wang, Xiaolu Warfield, Becka M. Kueh, Andrew J. Voss, Anne K. Thomas, Tim Garcia, Benjamin A. Liu, Wenshe R. Strahl, Brian D. Kono, Hidetoshi Li, Wei Shi, Xiaobing Côté, Jacques Kutateladze, Tatiana G. |
author_sort | Klein, Brianna J. |
collection | PubMed |
description | Acetylation of histone H3K23 has emerged as an essential posttranslational modification associated with cancer and learning and memory impairment, yet our understanding of this epigenetic mark remains insufficient. Here, we identify the native MORF complex as a histone H3K23-specific acetyltransferase and elucidate its mechanism of action. The acetyltransferase function of the catalytic MORF subunit is positively regulated by the DPF domain of MORF (MORF(DPF)). The crystal structure of MORF(DPF) in complex with crotonylated H3K14 peptide provides mechanistic insight into selectivity of this epigenetic reader and its ability to recognize both histone and DNA. ChIP data reveal the role of MORF(DPF) in MORF-dependent H3K23 acetylation of target genes. Mass spectrometry, biochemical and genomic analyses show co-existence of the H3K23ac and H3K14ac modifications in vitro and co-occupancy of the MORF complex, H3K23ac, and H3K14ac at specific loci in vivo. Our findings suggest a model in which interaction of MORF(DPF) with acylated H3K14 promotes acetylation of H3K23 by the native MORF complex to activate transcription. |
format | Online Article Text |
id | pubmed-6797804 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-67978042019-10-21 Histone H3K23-specific acetylation by MORF is coupled to H3K14 acylation Klein, Brianna J. Jang, Suk Min Lachance, Catherine Mi, Wenyi Lyu, Jie Sakuraba, Shun Krajewski, Krzysztof Wang, Wesley W. Sidoli, Simone Liu, Jiuyang Zhang, Yi Wang, Xiaolu Warfield, Becka M. Kueh, Andrew J. Voss, Anne K. Thomas, Tim Garcia, Benjamin A. Liu, Wenshe R. Strahl, Brian D. Kono, Hidetoshi Li, Wei Shi, Xiaobing Côté, Jacques Kutateladze, Tatiana G. Nat Commun Article Acetylation of histone H3K23 has emerged as an essential posttranslational modification associated with cancer and learning and memory impairment, yet our understanding of this epigenetic mark remains insufficient. Here, we identify the native MORF complex as a histone H3K23-specific acetyltransferase and elucidate its mechanism of action. The acetyltransferase function of the catalytic MORF subunit is positively regulated by the DPF domain of MORF (MORF(DPF)). The crystal structure of MORF(DPF) in complex with crotonylated H3K14 peptide provides mechanistic insight into selectivity of this epigenetic reader and its ability to recognize both histone and DNA. ChIP data reveal the role of MORF(DPF) in MORF-dependent H3K23 acetylation of target genes. Mass spectrometry, biochemical and genomic analyses show co-existence of the H3K23ac and H3K14ac modifications in vitro and co-occupancy of the MORF complex, H3K23ac, and H3K14ac at specific loci in vivo. Our findings suggest a model in which interaction of MORF(DPF) with acylated H3K14 promotes acetylation of H3K23 by the native MORF complex to activate transcription. Nature Publishing Group UK 2019-10-17 /pmc/articles/PMC6797804/ /pubmed/31624313 http://dx.doi.org/10.1038/s41467-019-12551-5 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Klein, Brianna J. Jang, Suk Min Lachance, Catherine Mi, Wenyi Lyu, Jie Sakuraba, Shun Krajewski, Krzysztof Wang, Wesley W. Sidoli, Simone Liu, Jiuyang Zhang, Yi Wang, Xiaolu Warfield, Becka M. Kueh, Andrew J. Voss, Anne K. Thomas, Tim Garcia, Benjamin A. Liu, Wenshe R. Strahl, Brian D. Kono, Hidetoshi Li, Wei Shi, Xiaobing Côté, Jacques Kutateladze, Tatiana G. Histone H3K23-specific acetylation by MORF is coupled to H3K14 acylation |
title | Histone H3K23-specific acetylation by MORF is coupled to H3K14 acylation |
title_full | Histone H3K23-specific acetylation by MORF is coupled to H3K14 acylation |
title_fullStr | Histone H3K23-specific acetylation by MORF is coupled to H3K14 acylation |
title_full_unstemmed | Histone H3K23-specific acetylation by MORF is coupled to H3K14 acylation |
title_short | Histone H3K23-specific acetylation by MORF is coupled to H3K14 acylation |
title_sort | histone h3k23-specific acetylation by morf is coupled to h3k14 acylation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797804/ https://www.ncbi.nlm.nih.gov/pubmed/31624313 http://dx.doi.org/10.1038/s41467-019-12551-5 |
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