DAXX adds a de novo H3.3K9me3 deposition pathway to the histone chaperone network

Massimo Carraro, Ivo A. Hendriks, Colin M. Hammond, Victor Solis-Mezarino, Moritz Völker-Albert, Jonas D. Elsborg, Melanie B. Weisser, Christos Spanos, Guillermo Montoya, Juri Rappsilber, Axel Imhof, Michael L. Nielsen, Anja Groth

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Pages (from-to)1075-1092.e9
Number of pages18
JournalMolecular Cell
Issue number7
Early online date2 Mar 2023
Publication statusPublished - 6 Apr 2023

Keywords / Materials (for Non-textual outputs)

  • ASF1
  • DAXX
  • NASP
  • histone chaperone
  • protein network
  • nucleosome assembly
  • heterochromatin
  • gene silencing
  • proteomics
  • epigenetic


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