Chang Sun

All Publications

• The histone chaperone function of Daxx is dispensable for embryonic development CELL DEATH & DISEASE Sun, C., Qi, Y., Fowlkes, N., Lazic, N., Su, X., Lozano, G., Wasylishen, A. R. 2023; 14 (8): 565

  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 (DaxxY130A), and Daxx and H3.3 (DaxxS226A). 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.

  View details for DOI 10.1038/s41419-023-06089-0

  View details for Web of Science ID 001093874500003

  View details for PubMedID 37633949

  View details for PubMedCentralID PMC10460429

• Tissue specificity and spatio-temporal dynamics of the p53 transcriptional program CELL DEATH AND DIFFERENTIATION Pant, V., Sun, C., Lozano, G. 2023; 30 (4): 897-905

  Abstract

  Transcription factors regulate hundreds of genes and p53 is no exception. As a stress responsive protein, p53 transactivates an array of downstream targets which define its role in maintaining physiological functions of cells/tissues. Despite decades of studies, our understanding of the p53 in vivo transcriptional program is still incomplete. Here we discuss some of the physiological stressors that activate p53, the pathological and physiological implications of p53 activation and the molecular profiling of the p53 transcriptional program in maintaining tissue homeostasis. We argue that the p53 transcriptional program is spatiotemporally regulated in a tissue-specific manner and define a p53 target signature that faithfully depicts p53 activity. We further emphasize that additional in vivo studies are needed to refine the p53 transactivation profile to harness it for therapeutic purposes.

  View details for DOI 10.1038/s41418-023-01123-2

  View details for Web of Science ID 000940749200001

  View details for PubMedID 36755072

  View details for PubMedCentralID PMC10070629