Nucleosome conformation dictates the histone code
- EpiCypher, United States
- University of Colorado Anschutz Medical Campus, United States
- University of North Carolina at Chapel Hill, United States
Abstract
Histone post-translational modifications (PTMs) play a critical role in chromatin regulation. It has been proposed that these PTMs form localized 'codes' that are read by specialized regions (reader domains) in chromatin associated proteins (CAPs) to regulate downstream function. Substantial effort has been made to define [CAP : histone PTM] specificities, and thus decipher the histone code and guide epigenetic therapies. However, this has largely been done using the reductive approach of isolated reader domains and histone peptides, which cannot account for any higher order factors. Here we show that the [BPTF PHD finger and bromodomain : histone PTM] interaction is dependent on nucleosome context. The tandem reader selectively associates with nucleosomal H3K4me3 and H3K14ac or H3K18ac, a combinatorial engagement that despite being in cis is not predicted by peptides. This in vitro specificity of the BPTF tandem reader for PTM-defined nucleosomes is recapitulated in a cellular context. We propose that regulatable histone tail accessibility and its impact on the binding potential of reader domains necessitates we refine the 'histone code' concept and interrogate it at the nucleosome level.
Data availability
Raw data from dCypher assays is in Supplementary File 1. All sequencing data has been deposited in the NCBU Gene Expression Omnibus (GEO) with accession number GSE150617.
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Nucleosome conformation dictates the histone codeNCBI Gene Expression Omnibus, GSE150617.
Article and author information
Author details
Eileen T McAnarney
Krzysztof Krajewski
Catherine A Musselman
Funding
National Institutes of Health (2T32GM008365-26A1)
- Harrison A Fuchs
National Institutes of Health (P30CA086862)
- Catherine A Musselman
National Science Foundation (CAREER-1452411)
- Harrison A Fuchs
National Institutes of Health (R35GM128705)
- Harrison A Fuchs
- Catherine A Musselman
National Institutes of Health (R43CA236474)
- Matthew R Marunde
- Jonathan M Burg
- Irina K Popova
- Anup Vaidya
- Nathan W Hall
- Ellen N Weinzapfel
- Matthew J Meiners
- Rachel Watson
- Zachary B Gillespie
- Hailey F Taylor
- Laylo Mukhsinova
- Ugochi C Onuoha
- Sarah A Howard
- Katherine Novitzky
- Eileen T McAnarney
- Krzysztof Krajewski
- Martis W Cowles
- Marcus A Cheek
- Zu-Wen Sun
- Bryan J Venters
- Michael-C Keogh
National Institutes of Health (R44GM117683)
- Matthew R Marunde
- Jonathan M Burg
- Irina K Popova
- Anup Vaidya
- Nathan W Hall
- Ellen N Weinzapfel
- Matthew J Meiners
- Rachel Watson
- Zachary B Gillespie
- Hailey F Taylor
- Laylo Mukhsinova
- Ugochi C Onuoha
- Sarah A Howard
- Katherine Novitzky
- Eileen T McAnarney
- Krzysztof Krajewski
- Martis W Cowles
- Marcus A Cheek
- Zu-Wen Sun
- Bryan J Venters
- Michael-C Keogh
National Institutes of Health (R44CA214076)
- Matthew R Marunde
- Jonathan M Burg
- Irina K Popova
- Anup Vaidya
- Nathan W Hall
- Ellen N Weinzapfel
- Matthew J Meiners
- Rachel Watson
- Zachary B Gillespie
- Hailey F Taylor
- Laylo Mukhsinova
- Ugochi C Onuoha
- Sarah A Howard
- Katherine Novitzky
- Eileen T McAnarney
- Krzysztof Krajewski
- Martis W Cowles
- Marcus A Cheek
- Zu-Wen Sun
- Bryan J Venters
- Michael-C Keogh
National Institutes of Health (R44GM116584)
- Matthew R Marunde
- Jonathan M Burg
- Irina K Popova
- Anup Vaidya
- Nathan W Hall
- Ellen N Weinzapfel
- Matthew J Meiners
- Rachel Watson
- Zachary B Gillespie
- Hailey F Taylor
- Laylo Mukhsinova
- Ugochi C Onuoha
- Sarah A Howard
- Katherine Novitzky
- Eileen T McAnarney
- Krzysztof Krajewski
- Martis W Cowles
- Marcus A Cheek
- Zu-Wen Sun
- Bryan J Venters
- Michael-C Keogh
National Institutes of Health (R44DE029633)
- Matthew R Marunde
- Jonathan M Burg
- Irina K Popova
- Anup Vaidya
- Nathan W Hall
- Ellen N Weinzapfel
- Matthew J Meiners
- Rachel Watson
- Zachary B Gillespie
- Hailey F Taylor
- Laylo Mukhsinova
- Ugochi C Onuoha
- Sarah A Howard
- Katherine Novitzky
- Eileen T McAnarney
- Krzysztof Krajewski
- Martis W Cowles
- Marcus A Cheek
- Zu-Wen Sun
- Bryan J Venters
- Michael-C Keogh
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2024, Marunde et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Nucleosome conformation dictates the histone code
eLife 13:e78866.
https://doi.org/10.7554/eLife.78866
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