| Structural highlights
Function
HPC2_YEAST Component of the HIR complex, which functions as a histone chaperone that 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.[1] [2] [3]
Publication Abstract from PubMed
The evolutionarily conserved HIRA/Hir histone chaperone complex and ASF1a/Asf1 co-chaperone cooperate to deposit histone (H3/H4)(2) tetramers on DNA for replication-independent chromatin assembly. The molecular architecture of the HIRA/Hir complex and its mode of histone deposition have remained unknown. Here, we report the cryo-EM structure of the S. cerevisiae Hir complex with Asf1/H3/H4 at 2.9-6.8 A resolution. We find that the Hir complex forms an arc-shaped dimer with a Hir1/Hir2/Hir3/Hpc2 stoichiometry of 2/4/2/4. The core of the complex containing two Hir1/Hir2/Hir2 trimers and N-terminal segments of Hir3 forms a central cavity containing two copies of Hpc2, with one engaged by Asf1/H3/H4, in a suitable position to accommodate a histone (H3/H4)(2) tetramer, while the C-terminal segments of Hir3 harbor nucleic acid binding activity to wrap DNA around the Hpc2-assisted histone tetramer. The structure suggests a model for how the Hir/Asf1 complex promotes the formation of histone tetramers for their subsequent deposition onto DNA.
Structure of the Hir histone chaperone complex.,Kim HJ, Szurgot MR, van Eeuwen T, Ricketts MD, Basnet P, Zhang AL, Vogt A, Sharmin S, Kaplan CD, Garcia BA, Marmorstein R, Murakami K Mol Cell. 2024 Jun 20:S1097-2765(24)00478-7. doi: 10.1016/j.molcel.2024.05.031. PMID:38925115[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Formosa T, Ruone S, Adams MD, Olsen AE, Eriksson P, Yu Y, Rhoades AR, Kaufman PD, Stillman DJ. Defects in SPT16 or POB3 (yFACT) in Saccharomyces cerevisiae cause dependence on the Hir/Hpc pathway: polymerase passage may degrade chromatin structure. Genetics. 2002 Dec;162(4):1557-71. PMID:12524332
- ↑ Prochasson P, Florens L, Swanson SK, Washburn MP, Workman JL. The HIR corepressor complex binds to nucleosomes generating a distinct protein/DNA complex resistant to remodeling by SWI/SNF. Genes Dev. 2005 Nov 1;19(21):2534-9. PMID:16264190 doi:10.1101/gad.1341105
- ↑ Green EM, Antczak AJ, Bailey AO, Franco AA, Wu KJ, Yates JR 3rd, Kaufman PD. Replication-independent histone deposition by the HIR complex and Asf1. Curr Biol. 2005 Nov 22;15(22):2044-9. PMID:16303565 doi:http://dx.doi.org/S0960-9822(05)01306-0
- ↑ Kim HJ, Szurgot MR, van Eeuwen T, Ricketts MD, Basnet P, Zhang AL, Vogt A, Sharmin S, Kaplan CD, Garcia BA, Marmorstein R, Murakami K. Structure of the Hir histone chaperone complex. Mol Cell. 2024 Jun 20:S1097-2765(24)00478-7. PMID:38925115 doi:10.1016/j.molcel.2024.05.031
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