Year: 2023
Type: article
Abstract: A multitude of histone chaperones are required to support histones from their biosynthesis until DNA deposition. They cooperate through the formation of histone co-chaperone complexes, but the crosstalk between nucleosome assembly pathways remains enigmatic. Using exploratory interactomics, we define the interplay between human histone H3-H4 chaperones in the histone chaperone network. We identify previously uncharacterized 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 provides a unique functionality to the histone chaperone network, recruiting histone methyltransferases to promote H3K9me3 catalysis on new histone H3.3-H4 prior to deposition onto DNA. Hereby, DAXX provides a molecular mechanism for de novo H3K9me3 deposition and heterochromatin assembly. Collectively, our findings provide a framework for understanding how cells orchestrate histone supply and employ targeted deposition of modified histones to underpin specialized chromatin states.
Source: Molecular Cell
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $9,080
Funders: Kræftens Bekæmpelse, Wellcome Trust, European Commission, Deutsche Forschungsgemeinschaft, Københavns Universitet, Lundbeckfonden, Novo Nordisk, Novo Nordisk Fonden, Danmarks Frie Forskningsfond, H. Lundbeck A/S, Horizon 2020 Framework Programme, European Research Council, Horizon 2020, H2020 European Research Council
Awards: G1076064052, G1303691827, G1717371286, European Proteomics Infrastructure Consortium providing Access, SFB 1064: Chromatindynamik, G2291518063, G2521130840, G3198518641, G3239613150, G3443399178, G3547480303, G3606019796, G3658199024, G3693516624, G4282887365, G434337789, G4419098916, G4440794354, SFB 1309: Chemische Biologie epigenetischer Modifikationen, G475513623, G485221048, New and Old Histones in Epigenetic Cell Memory, G5734189366, G5875395564, G6531441707, G7317896566, G7580957167, G7618893879, Core Funding for the Wellcome Trust Centre for Cell Biology
OpenAlex ID: W4322775905