Histone H4 lysine 20 mono-methylation directly facilitates chromatin openness and promotes transcription of housekeeping genes
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- Histone H4 lysine 20 mono-methylation directly facilitates chromatin openness and promotes transcription of housekeeping genes
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Histone lysine methylations have primarily been linked to selective recruitment of reader or effector proteins that subsequently modify chromatin regions and mediate genome functions. Here, we describe a divergent role for histone H4 lysine 20 mono-methylation (H4K20me1) and demonstrate that it directly facilitates chromatin openness and accessibility by disrupting chromatin folding. Thus, accumulation of H4K20me1 demarcates highly accessible chromatin at genes, and this is maintained throughout the cell cycle. In vitro, H4K20me1-containing nucleosomal arrays with nucleosome repeat lengths (NRL) of 187 and 197 are less compact than unmethylated (H4K20me0) or trimethylated (H4K20me3) arrays. Concordantly, and in contrast to trimethylated and unmethylated tails, solid-state NMR data shows that H4K20 mono-methylation changes the H4 conformational state and leads to more dynamic histone H4-tails. Notably, the increased chromatin accessibility mediated by H4K20me1 facilitates gene expression, particularly of housekeeping genes. Altogether, we show how the methylation state of a single histone H4 residue operates as a focal point in chromatin structure control. While H4K20me1 directly promotes chromatin openness at highly transcribed genes, it also serves as a stepping-stone for H4K20me3-dependent chromatin compaction.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 4800 |
| Tidsskrift | Nature Communications |
| Vol/bind | 12 |
| Udgave nummer | 1 |
| Antal sider | 16 |
| ISSN | 2041-1723 |
| DOI | |
| Status | Udgivet - 2021 |
Bibliografisk note
Funding Information:
We are highly grateful to Dr. Nikolay Korolev for valuable discussions. We are highly grateful to Prof. Kristian Helin and Dr. Paul Cloos for critical reading of the manuscript. We are thankful to Dr. Heike Ilona Rösner for helpful discussions in the early stages of the project. The plasmid constructs for 15-197-601, 16-187-601, and 12-202-601 DNA were kindly provided by Prof. Daniela Rhodes. We are thankful to Jens Vilstrup Johansen at BRIC bioinformatics core facility for pre-processing of the ChIP-seq and ATAC-seq datasets. Work in the CSS laboratory was supported by the Novo Nordisk Foundation, Benzon foundation, and the Danish Cancer Society. We thank the Danish National Research Foundation for grant DNRF115 funding the Center for Chromosome Stability. The Singapore Ministry of Education Academic Research Fund (AcRF) Tier 2 (MOE2018-T2-1-112) and Tier 1 (2018-T1-001-114) grants supported work in the LN laboratory. All ssNMR experiments were performed at the Nanyang Technological University (NTU) Center of High-Field NMR Spectroscopy and Imaging. We also acknowledge the NTU Institute of Structural Biology (NISB) for supporting this research. ChIP-sequencing was performed at the Bioinformatics and Expression Analysis (BEA) core facility at KI, which is supported by the board of research at the Karolinska Institutet and the research committee at the Karolinska Hospital, ChIP samples were prepared by Christos Coucaravas. Work in the KE laboratory was supported by the Swedish Research Council and Cancerfonden.
Publisher Copyright:
© 2021, The Author(s).
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