| Structural highlights
Function
HIR1_YEAST Component of the HIR complex, which 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] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19]
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[20]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Dimova D, Nackerdien Z, Furgeson S, Eguchi S, Osley MA. A role for transcriptional repressors in targeting the yeast Swi/Snf complex. Mol Cell. 1999 Jul;4(1):75-83. PMID:10445029 doi:10.1016/s1097-2765(00)80189-6
- ↑ Sutton A, Bucaria J, Osley MA, Sternglanz R. Yeast ASF1 protein is required for cell cycle regulation of histone gene transcription. Genetics. 2001 Jun;158(2):587-96. PMID:11404324
- ↑ Sharp JA, Fouts ET, Krawitz DC, Kaufman PD. Yeast histone deposition protein Asf1p requires Hir proteins and PCNA for heterochromatic silencing. Curr Biol. 2001 Apr 3;11(7):463-73. PMID:11412995
- ↑ Krawitz DC, Kama T, Kaufman PD. Chromatin assembly factor I mutants defective for PCNA binding require Asf1/Hir proteins for silencing. Mol Cell Biol. 2002 Jan;22(2):614-25. PMID:11756556
- ↑ Sharp JA, Franco AA, Osley MA, Kaufman PD. Chromatin assembly factor I and Hir proteins contribute to building functional kinetochores in S. cerevisiae. Genes Dev. 2002 Jan 1;16(1):85-100. PMID:11782447 doi:10.1101/gad.925302
- ↑ Ng HH, Robert F, Young RA, Struhl K. Genome-wide location and regulated recruitment of the RSC nucleosome-remodeling complex. Genes Dev. 2002 Apr 1;16(7):806-19. PMID:11937489 doi:10.1101/gad.978902
- ↑ 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
- ↑ Sharp JA, Krawitz DC, Gardner KA, Fox CA, Kaufman PD. The budding yeast silencing protein Sir1 is a functional component of centromeric chromatin. Genes Dev. 2003 Oct 1;17(19):2356-61. PMID:12975325 doi:10.1101/gad.1131103
- ↑ Crotti LB, Basrai MA. Functional roles for evolutionarily conserved Spt4p at centromeres and heterochromatin in Saccharomyces cerevisiae. EMBO J. 2004 Apr 21;23(8):1804-14. Epub 2004 Apr 1. PMID:15057281 doi:http://dx.doi.org/10.1038/sj.emboj.7600161
- ↑ Sharp JA, Rizki G, Kaufman PD. Regulation of histone deposition proteins Asf1/Hir1 by multiple DNA damage checkpoint kinases in Saccharomyces cerevisiae. Genetics. 2005 Nov;171(3):885-99. Epub 2005 Jul 14. PMID:16020781 doi:http://dx.doi.org/10.1534/genetics.105.044719
- ↑ Schermer UJ, Korber P, Horz W. Histones are incorporated in trans during reassembly of the yeast PHO5 promoter. Mol Cell. 2005 Jul 22;19(2):279-85. PMID:16039596 doi:http://dx.doi.org/10.1016/j.molcel.2005.05.028
- ↑ 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
- ↑ Nourani A, Robert F, Winston F. Evidence that Spt2/Sin1, an HMG-like factor, plays roles in transcription elongation, chromatin structure, and genome stability in Saccharomyces cerevisiae. Mol Cell Biol. 2006 Feb;26(4):1496-509. PMID:16449659 doi:10.1128/MCB.26.4.1496-1509.2006
- ↑ Sherwood PW, Tsang SV, Osley MA. Characterization of HIR1 and HIR2, two genes required for regulation of histone gene transcription in Saccharomyces cerevisiae. Mol Cell Biol. 1993 Jan;13(1):28-38. PMID:8417331 doi:10.1128/mcb.13.1.28-38.1993
- ↑ Spector MS, Raff A, DeSilva H, Lee K, Osley MA. Hir1p and Hir2p function as transcriptional corepressors to regulate histone gene transcription in the Saccharomyces cerevisiae cell cycle. Mol Cell Biol. 1997 Feb;17(2):545-52. PMID:9001207 doi:10.1128/MCB.17.2.545
- ↑ DeSilva H, Lee K, Osley MA. Functional dissection of yeast Hir1p, a WD repeat-containing transcriptional corepressor. Genetics. 1998 Feb;148(2):657-67. PMID:9504914 doi:10.1093/genetics/148.2.657
- ↑ Qian Z, Huang H, Hong JY, Burck CL, Johnston SD, Berman J, Carol A, Liebman SW. Yeast Ty1 retrotransposition is stimulated by a synergistic interaction between mutations in chromatin assembly factor I and histone regulatory proteins. Mol Cell Biol. 1998 Aug;18(8):4783-92. PMID:9671488 doi:10.1128/MCB.18.8.4783
- ↑ Kaufman PD, Cohen JL, Osley MA. Hir proteins are required for position-dependent gene silencing in Saccharomyces cerevisiae in the absence of chromatin assembly factor I. Mol Cell Biol. 1998 Aug;18(8):4793-806. PMID:9671489 doi:10.1128/MCB.18.8.4793
- ↑ 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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