Fig. 2: Characteristics of H3.3 and its chaperones, HIRA, and DAXX complexes.

a Structure of the H3.3-containing nucleosome. Within the 5 amino acids that distinguish H3.3 from H3.1, the AIG motif (A87, I89, and G90) is recognized by UBN1/2 among the HIRA-interacting proteins or by DAXX. These variant-specific chaperones have distinct roles in depositing H3.3 in specific chromosomal regions: the HIRA complex contributes to H3.3 addition in euchromatin regions, while the DAXX/ATRX complex facilitates H3.3 deposition in telomeres, pericentromeric repeats, and other heterochromatic areas. b The functional domains of HIRA-interacting proteins for their chaperone activity. H3.3 interacts with the HRD and N-terminal core domains of UBN1 and ASF1, respectively. c The functional domains of ATRX and DAXX. H3.3 interacts with the HBD of DAXX. WD40 repeat Trp-Asp 40 repeat, Hir histone regulatory, NHRD nucleotide-binding and helical repeat domain, HRD helical repeat domain, M middle domain, TPR repeat tetratricopeptide repeat, SIM sumo-interaction motif, 4HB four-helix bundle, HBD histone-binding domain, ADD domain ATRX-DNMT3-DNMT3L domain, HP1 HP1-binding motif (PxVxL).