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DAXX adds a de novo H3.3K9me3 deposition pathway to the histone chaperone network
Open accessPreprint — published as 10.1016/j.molcel.2023.02.009
Abstract
SUMMARY: A multitude of histone chaperones are required to protect histones after their biosynthesis until DNA deposition. They cooperate through the formation of co-chaperone complexes, but the crosstalk between nucleosome assembly pathways remains enigmatic. Using explorative interactomics approaches, we characterize the organization of the histone H3–H4 chaperones network and define the interplay between histone chaperone systems. We identify and validate several novel histone dependent complexes and predict the structure of the ASF1 and SPT2 co-chaperone complex, expanding the role of ASF1 in histone dynamics. We show that DAXX acts separately from the rest of the network, recruiting heterochromatin factors and promoting lysine 9 tri-methylation of new histone H3.3 prior to deposition onto DNA. With its functionality, DAXX provides a molecular mechanism for de novo heterochromatin assembly. Collectively, our findings provide a new framework for understanding how cells orchestrate histone supply and comply with chromatin dynamics throughout the cell cycle.
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Metadata
- Authors
- Carraro, M., Hendriks, I. A., Hammond, C. M., Solis, V., Völker-Albert, M., Elsborg, J. D., Weisser, M. B., Spanos, C., Montoya, G., Rappsilber, J., Imhof, A., Nielsen, M. L., & Groth, A.
- Affiliations
- University of Copenhagen (DK)
- Wellcome Centre for Cell Biology (GB)
- Ludwig-Maximilians-Universität München (DE)
- Corresponding author
- Hammond, Colin M.
- Nielsen, Michael L.
- Groth, Anja
- ORCID
- Venue
- Molecular Cell
- Publisher
- openRxiv
- Published
- 2022-09-20
- Volume
- 83
- Issue
- 7
- Pages
- 1075-1092.e9
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC10114496
- OpenAlex
- W4322775905
- Cited by
- 62
- References
- 1
- Citations by year
- 2026: 16 · 2025: 11 · 2024: 22 · 2023: 13
- FWCI
- 5.52
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Molecular Cell (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- Funders
- Kræftens Bekæmpelse (R146-A9159, R146-A9159-16-S2)
- Wellcome Trust (823839, 203149)
- European Commission (823839, HORIZON2020)
- Deutsche Forschungsgemeinschaft (213249687, CRC 1064, 203149, 325871075, NNF0024386, NNF17SA00302140, CRC1309, NNF18OC0055061)
- Københavns Universitet
- Lundbeckfonden (R198-2015-269, NNF14CC0001, 724436, R313-2019-448, 7016-00042B)
- Novo Nordisk (NNF14CC0001, NNF18OC0055061)
- Novo Nordisk Fonden (NNF 14CC0001, NNF0024386, NNF18OC0055061, NNF21OC0067425)
- Danmarks Frie Forskningsfond (0135-00096B, 8020-00220B)
- H. Lundbeck A/S
- Horizon 2020 Framework Programme
- European Research Council
- Horizon 2020 (EPIC-XS-823839)
- H2020 European Research Council (724436)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- DAXX, histone chaperone, histone H3.3, H3K9me3, histone methyltransferase, Asf1, histone deposition, heterochromatin assembly, nucleosome assembly, histone dynamics, chromatin modification
- MeSH terms
- DNA, Histones, Humans, Nucleosomes, Cell Cycle Proteins, Molecular Chaperones, Histone Chaperones, Co-Repressor Proteins
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