UBR7 Acts as a Histone Chaperone That Promotes Reincorporation of Post-Nucleosomal Histone H3

Ferguson, Ann

doi:https://doi.org/10.21985/n2-a1wr-8v19

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UBR7 Acts as a Histone Chaperone That Promotes Reincorporation of Post-Nucleosomal Histone H3

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The eukaryotic genome is packaged into chromatin. The nucleosome, the basic unit of chromatin, is composed of DNA coiled around a histone octamer. Histones are among the longest-lived protein species in mammalian cells, due to their thermodynamic stability and their associations with DNA and histone chaperones. Histone metabolism plays an integral role in homeostasis. While histones are largely stable, degradation of histone proteins is necessary under specific conditions. Here we first review the physiological and cellular contexts which promote histone degradation and describe specific known mechanisms that drive histone proteolysis. We discuss the importance of histone metabolism and regulation of histone supply for organismal and cellular fitness. Histone chaperones modulate the stability of histones beginning from histone synthesis, through incorporation into DNA, and facilitate histone retention during transcription and replication. Following histone removal from DNA, chaperones regulate histone storage, degradation, and reincorporation into chromatin. Here we characterize UBR7 as a histone H3.1 chaperone that modulates the supply of pre-existing post-nucleosomal histone complexes. UBR7 is a largely nuclear soluble protein. 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. The pool of NASP-bound post-nucleosomal histones accumulate in the absence of UBR7, and H3K4me3 is depleted from chromatin normally bound by UBR7. We performed a CRISPR-based genetic interaction screen which supports a link between UBR7 and pathways that interact with pre-existing histones. We propose that the interaction of UBR7, NASP, and histones opposes the histone storage functions of NASP, where UBR7 promotes reincorporation of post-nucleosomal H3 complexes into chromatin.

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