The HirA B (Histone regulatory homologue A binding) motif is the essential binding interface between and ASF1a, of approx. 40 residues. It forms an antiparallel β-hairpin that binds perpendicular to the strands of the β-sandwich of ASF1a N-terminal core domain, via β-sheet, salt bridge and van der Waals interactions []. The two histone chaperone proteins, HIRA and ASF1a, form a heterodimer with histones H3 and H4. HIRA is the human orthologue of Hir proteins known to silence histone gene expression and create transcriptionally silent heterochromatin in yeast, flies, plants and humans. The HIR complex is composed of HIR1, HIR2, HIR3 and HPC2, and interacts with ASF1. The HIR complex cooperates with ASF1 to promote replication-independent chromatin assembly. The HIR complex is also required for the periodic repression of three of the four histone gene loci during cell cycle as well as for autogenous regulation of the HTA1-HTB1 locus by H2A and H2B. DNA-binding by the HIR complex may repress transcription by inhibiting nucleosome remodeling by the SWI/SNF complex. The HIR complex may also be required for transcriptional silencing of centromeric, telomeric and mating-type loci in the absence of CAF-1.
HIRIP3 interacts with the HIRA histone chaperone []. It can be phosphorylated by the serine-threonine kinase CK2 and may be involved in chromatin metabolism [].
This entry represents ubinuclein-2 (UBN2). It contains a conserved HIRA-binding domain, which directly interacts with the N-terminal WD repeats of HIRA []. UBN2 and UBN1 are believed to be the orthologs of Hpc2p, a subunit of the HIR complex (a nucleosome assembly complex involved in regulation of histone gene transcription) in budding yeast []. It is phosphorylated upon DNA damage, probably by ATM or ATR [].
Ubinuclein-1 (UBN1) is part of the histone chaperone complex HIRA/UBN1/CABIN1/ASF1a that preferentially deposits the histone variant H3.3 into chromatin and is implicated in diverse chromatin regulatory events from gene activation to heterochromatinisation [, ].Ubinuclein-1 interacts with HIRA and is involved in the formation of senescence-associated heterochromatin foci (SAHF). SAHF are domains of specialised chromatin found in senescent cells that repress expression of proliferation-promoting genes [].
This entry includes NFU1-like proteins from eukaryotes and some uncharacterised proteins from prokaryotes.Nfu functions as a scaffold protein for assembly and delivery of rudimentary Fe-S clusters to target proteins [, ]. A human Nfu homologue, HIRA-interacting protein 5 (HIRIP5), was first identified in a two-hybrid screen for proteins that interact with the transcription regulator HIRA []. It seems that two human Nfu isoforms are generated by alternative explicing, which are subsequently targeted to different subcellular compartments [].
This entry includes HIR1/HIR2 from yeasts and HIRA from animals. They are WD-repeat containing proteins required for regulation of histone gene transcription. The budding yeast HIR complex is composed of Hir1, Hir2, Hir3 and Hpc2, and interacts with ASF1 [, ]. The HIR complex cooperates with ASF1 to promote replication-independent chromatin assembly. The HIR complex is also required for the periodic repression of three of the four histone gene loci during cell cycle as well as for autogenous regulation of the HTA1-HTB1 locus by H2A and H2B. DNA-binding by the HIR complex may repress transcription by inhibiting nucleosome remodeling by the SWI/SNF complex. The HIR complex may also be required for transcriptional silencing of centromeric, telomeric and mating-type loci in the absence of CAF-1 [].