An acetylation-mediated chromatin switch governs H3K4 methylation read-write capability
In nucleosomes, histone N-terminal tails exist in dynamic equilibrium between free/accessible and collapsed/DNA-bound states. The latter state is expected to impact histone N-termini availability to the epigenetic machinery. Notably, H3 tail acetylation (e.g. K9ac, K14ac, K18ac) is linked to increas...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2023-05-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/82596 |
| _version_ | 1797816519744290816 |
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| author | Kanishk Jain Matthew R Marunde Jonathan M Burg Susan L Gloor Faith M Joseph Karl F Poncha Zachary B Gillespie Keli L Rodriguez Irina K Popova Nathan W Hall Anup Vaidya Sarah A Howard Hailey F Taylor Laylo Mukhsinova Ugochi C Onuoha Emily F Patteson Spencer W Cooke Bethany C Taylor Ellen N Weinzapfel Marcus A Cheek Matthew J Meiners Geoffrey C Fox Kevin EW Namitz Martis W Cowles Krzysztof Krajewski Zu-Wen Sun Michael S Cosgrove Nicolas L Young Michael-Christopher Keogh Brian D Strahl |
| author_facet | Kanishk Jain Matthew R Marunde Jonathan M Burg Susan L Gloor Faith M Joseph Karl F Poncha Zachary B Gillespie Keli L Rodriguez Irina K Popova Nathan W Hall Anup Vaidya Sarah A Howard Hailey F Taylor Laylo Mukhsinova Ugochi C Onuoha Emily F Patteson Spencer W Cooke Bethany C Taylor Ellen N Weinzapfel Marcus A Cheek Matthew J Meiners Geoffrey C Fox Kevin EW Namitz Martis W Cowles Krzysztof Krajewski Zu-Wen Sun Michael S Cosgrove Nicolas L Young Michael-Christopher Keogh Brian D Strahl |
| author_sort | Kanishk Jain |
| collection | DOAJ |
| description | In nucleosomes, histone N-terminal tails exist in dynamic equilibrium between free/accessible and collapsed/DNA-bound states. The latter state is expected to impact histone N-termini availability to the epigenetic machinery. Notably, H3 tail acetylation (e.g. K9ac, K14ac, K18ac) is linked to increased H3K4me3 engagement by the BPTF PHD finger, but it is unknown if this mechanism has a broader extension. Here, we show that H3 tail acetylation promotes nucleosomal accessibility to other H3K4 methyl readers, and importantly, extends to H3K4 writers, notably methyltransferase MLL1. This regulation is not observed on peptide substrates yet occurs on the cis H3 tail, as determined with fully-defined heterotypic nucleosomes. In vivo, H3 tail acetylation is directly and dynamically coupled with cis H3K4 methylation levels. Together, these observations reveal an acetylation ‘chromatin switch’ on the H3 tail that modulates read-write accessibility in nucleosomes and resolves the long-standing question of why H3K4me3 levels are coupled with H3 acetylation. |
| first_indexed | 2024-03-13T08:39:53Z |
| format | Article |
| id | doaj.art-4578fc571e78426c9ad347f2e09aa9c9 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-13T08:39:53Z |
| publishDate | 2023-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-4578fc571e78426c9ad347f2e09aa9c92023-05-30T14:50:03ZengeLife Sciences Publications LtdeLife2050-084X2023-05-011210.7554/eLife.82596An acetylation-mediated chromatin switch governs H3K4 methylation read-write capabilityKanishk Jain0https://orcid.org/0000-0001-8039-0464Matthew R Marunde1Jonathan M Burg2Susan L Gloor3Faith M Joseph4Karl F Poncha5Zachary B Gillespie6Keli L Rodriguez7Irina K Popova8Nathan W Hall9Anup Vaidya10Sarah A Howard11Hailey F Taylor12Laylo Mukhsinova13Ugochi C Onuoha14Emily F Patteson15Spencer W Cooke16Bethany C Taylor17Ellen N Weinzapfel18Marcus A Cheek19Matthew J Meiners20Geoffrey C Fox21https://orcid.org/0000-0001-5898-0847Kevin EW Namitz22https://orcid.org/0000-0003-4434-1475Martis W Cowles23Krzysztof Krajewski24Zu-Wen Sun25Michael S Cosgrove26Nicolas L Young27https://orcid.org/0000-0002-3323-2815Michael-Christopher Keogh28https://orcid.org/0000-0002-2219-8623Brian D Strahl29https://orcid.org/0000-0002-4947-6259Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill of Medicine, Chapel Hill, United States; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, United StatesEpiCypher, Inc, Durham, United StatesEpiCypher, Inc, Durham, United StatesEpiCypher, Inc, Durham, United StatesVerna & Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, United StatesVerna & Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, United StatesEpiCypher, Inc, Durham, United StatesEpiCypher, Inc, Durham, United StatesEpiCypher, Inc, Durham, United StatesEpiCypher, Inc, Durham, United StatesEpiCypher, Inc, Durham, United StatesEpiCypher, Inc, Durham, United StatesEpiCypher, Inc, Durham, United StatesEpiCypher, Inc, Durham, United StatesEpiCypher, Inc, Durham, United StatesEpiCypher, Inc, Durham, United StatesDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill of Medicine, Chapel Hill, United StatesVerna & Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, United StatesEpiCypher, Inc, Durham, United StatesEpiCypher, Inc, Durham, United StatesEpiCypher, Inc, Durham, United StatesCurriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, United StatesPennsylvania State University, State College, United StatesEpiCypher, Inc, Durham, United StatesDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill of Medicine, Chapel Hill, United StatesEpiCypher, Inc, Durham, United StatesDepartment of Biochemistry and Molecular Biology, Upstate Medical University, Syracuse, United StatesVerna & Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, United StatesEpiCypher, Inc, Durham, United StatesDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill of Medicine, Chapel Hill, United States; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, United States; Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, United StatesIn nucleosomes, histone N-terminal tails exist in dynamic equilibrium between free/accessible and collapsed/DNA-bound states. The latter state is expected to impact histone N-termini availability to the epigenetic machinery. Notably, H3 tail acetylation (e.g. K9ac, K14ac, K18ac) is linked to increased H3K4me3 engagement by the BPTF PHD finger, but it is unknown if this mechanism has a broader extension. Here, we show that H3 tail acetylation promotes nucleosomal accessibility to other H3K4 methyl readers, and importantly, extends to H3K4 writers, notably methyltransferase MLL1. This regulation is not observed on peptide substrates yet occurs on the cis H3 tail, as determined with fully-defined heterotypic nucleosomes. In vivo, H3 tail acetylation is directly and dynamically coupled with cis H3K4 methylation levels. Together, these observations reveal an acetylation ‘chromatin switch’ on the H3 tail that modulates read-write accessibility in nucleosomes and resolves the long-standing question of why H3K4me3 levels are coupled with H3 acetylation.https://elifesciences.org/articles/82596chromatinH3K4 methylationreadershistone tail acetylationnucleosomeswriters |
| spellingShingle | Kanishk Jain Matthew R Marunde Jonathan M Burg Susan L Gloor Faith M Joseph Karl F Poncha Zachary B Gillespie Keli L Rodriguez Irina K Popova Nathan W Hall Anup Vaidya Sarah A Howard Hailey F Taylor Laylo Mukhsinova Ugochi C Onuoha Emily F Patteson Spencer W Cooke Bethany C Taylor Ellen N Weinzapfel Marcus A Cheek Matthew J Meiners Geoffrey C Fox Kevin EW Namitz Martis W Cowles Krzysztof Krajewski Zu-Wen Sun Michael S Cosgrove Nicolas L Young Michael-Christopher Keogh Brian D Strahl An acetylation-mediated chromatin switch governs H3K4 methylation read-write capability eLife chromatin H3K4 methylation readers histone tail acetylation nucleosomes writers |
| title | An acetylation-mediated chromatin switch governs H3K4 methylation read-write capability |
| title_full | An acetylation-mediated chromatin switch governs H3K4 methylation read-write capability |
| title_fullStr | An acetylation-mediated chromatin switch governs H3K4 methylation read-write capability |
| title_full_unstemmed | An acetylation-mediated chromatin switch governs H3K4 methylation read-write capability |
| title_short | An acetylation-mediated chromatin switch governs H3K4 methylation read-write capability |
| title_sort | acetylation mediated chromatin switch governs h3k4 methylation read write capability |
| topic | chromatin H3K4 methylation readers histone tail acetylation nucleosomes writers |
| url | https://elifesciences.org/articles/82596 |
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