UBR7 acts as a histone chaperone for post‐nucleosomal histone H3

Histone chaperones modulate the stability of histones beginning from histone synthesis, through incorporation into DNA, and during recycling during transcription and replication. Following histone removal from DNA, chaperones regulate histone storage and degradation. Here, we demonstrate that UBR7 is a histone H3.1 chaperone that modulates the supply of pre‐existing post‐nucleosomal histone complexes. We demonstrate that UBR7 binds to post‐nucleosomal H3K4me3 and H3K9me3 histones via its UBR box and PHD. UBR7 binds to the non‐nucleosomal histone chaperone NASP. In the absence of UBR7, the pool of NASP‐bound post‐nucleosomal histones accumulate and chromatin is depleted of H3K4me3‐modified histones. We propose that the interaction of UBR7 with NASP and histones opposes the histone storage functions of NASP and that UBR7 promotes reincorporation of post‐nucleosomal H3 complexes. SYNOPSIS Histone chaperones facilitate deposition and recycling of histones. Here, UBR7 is found as a new chaperone recognizing post‐nucleosomal H3.1 and promoting its reincorporation, with implications for maintenance of epigenetic information. UBR7 binds non‐nucleosomal histone H3.1. The UBR7 PHD binds soluble histones methylated on Lys4 or Lys9, representing pre‐existing histone H3. UBR7 associates with the histone chaperone NASP. UBR7 opposes soluble H3/H4 buffering by NASP and promotes reincorporation of post‐nucleosomal histone H3. Graphical Abstract An unsuspected UBR7 function in recognition of displaced methylated histones opposes their storage by NASP, instead promoting their reincorporation into chromatin.