Cell Death and Disease (Aug 2023)

The histone chaperone function of Daxx is dispensable for embryonic development

  • Chang Sun,
  • Yuan Qi,
  • Natalie Fowlkes,
  • Nina Lazic,
  • Xiaoping Su,
  • Guillermina Lozano,
  • Amanda R. Wasylishen

DOI
https://doi.org/10.1038/s41419-023-06089-0
Journal volume & issue
Vol. 14, no. 8
pp. 1 – 9

Abstract

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Abstract Daxx functions as a histone chaperone for the histone H3 variant, H3.3, and is essential for embryonic development. Daxx interacts with Atrx to form a protein complex that deposits H3.3 into heterochromatic regions of the genome, including centromeres, telomeres, and repeat loci. To advance our understanding of histone chaperone activity in vivo, we developed two Daxx mutant alleles in the mouse germline, which abolish the interactions between Daxx and Atrx (Daxx Y130A ), and Daxx and H3.3 (Daxx S226A ). We found that the interaction between Daxx and Atrx is dispensable for viability; mice are born at the expected Mendelian ratio and are fertile. The loss of Daxx-Atrx interaction, however, does cause dysregulated expression of endogenous retroviruses. In contrast, the interaction between Daxx and H3.3, while not required for embryonic development, is essential for postnatal viability. Transcriptome analysis of embryonic tissues demonstrates that this interaction is important for silencing endogenous retroviruses and for maintaining proper immune cell composition. Overall, these results clearly demonstrate that Daxx has both Atrx-dependent and independent functions in vivo, advancing our understanding of this epigenetic regulatory complex.