The histone chaperone function of Daxx is dispensable for embryonic development

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 unde...

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Bibliographic Details
Published in:Cell death & disease 2023-08, Vol.14 (8), p.565-9, Article 565
Main Authors: Sun, Chang, Qi, Yuan, Fowlkes, Natalie, Lazic, Nina, Su, Xiaoping, Lozano, Guillermina, Wasylishen, Amanda R.
Format: Article
Language:English
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Adapter proteins
Alleles
Animals
Antibodies
Apoptosis
Biochemistry
Biology
Biomedical and Life Sciences
Cancer
Cell Biology
Cell Culture
Centromere
Centromeres
Co-Repressor Proteins - genetics
Daxx protein
Embryogenesis
Embryonic Development - genetics
Embryos
Epigenetics
Female
Genomes
Histone Chaperones - genetics
Histone H3
Histones
Immunology
Life Sciences
Mice
Molecular Chaperones - genetics
Mutation
Pregnancy
Telomeres
Transcriptomes
Tumors
Weaning
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Summary: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.
ISSN:2041-4889
2041-4889
DOI:10.1038/s41419-023-06089-0