Structural highlights
Function
[ASF1_SCHPO] Histone chaperone that facilitates histone deposition and histone exchange and removal during nucleosome assembly and disassembly.[1] [HIR1_SCHPO] Probably required for replication-independent chromatin assembly. Required for transcriptional silencing in the outer repeat (otr) centromeric repeats and the Tf2 long terminal repeat retrotransposons. Repressor of histone gene transcription in G1 arrested cells. Required for repression of htb1 gene expression outside of S phase.[2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The assembly of core histones onto eukaryotic DNA is modulated by several histone chaperone complexes, including Asf1, CAF-1, and HIRA. Asf1 is a unique histone chaperone that participates in both the replication-dependent and replication-independent pathways. Here we report the crystal structures of the apo-form of fission yeast Asf1/Cia1 (SpAsf1N; residues 1-161) as well as its complexes with the B-domain of the fission yeast HIRA orthologue Hip1 (Hip1B) and the C-terminal region of the Cac2 subunit of CAF-1 (Cac2C). The mode of the fission yeast Asf1N-Hip1B recognition is similar to that of the human Asf1-HIRA recognition, suggesting that Asf1N recognition of Hip1B/HIRA is conserved from yeast to mammals. Interestingly, Hip1B and Cac2C show remarkably similar interaction modes with Asf1. The binding between Asf1N and Hip1B was almost completely abolished by the D37A and L60A/V62A mutations in Asf1N, indicating the critical role of salt bridge and van der Waals contacts in the complex formation. Consistently, both of the aforementioned Asf1 mutations also drastically reduced the binding to Cac2C. These results provide a structural basis for a mutually exclusive Asf1-binding model of CAF-1 and HIRA/Hip1, in which Asf1 and CAF-1 assemble histones H3/H4 (H3.1/H4 in vertebrates) in a replication-dependent pathway, whereas Asf1 and HIRA/Hip1 assemble histones H3/H4 (H3.3/H4 in vertebrates) in a replication-independent pathway.
Crystal structures of fission yeast histone chaperone Asf1 complexed with the Hip1 B-domain or the Cac2 C terminus.,Malay AD, Umehara T, Matsubara-Malay K, Padmanabhan B, Yokoyama S J Biol Chem. 2008 May 16;283(20):14022-31. Epub 2008 Mar 11. PMID:18334479[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Umehara T, Chimura T, Ichikawa N, Horikoshi M. Polyanionic stretch-deleted histone chaperone cia1/Asf1p is functional both in vivo and in vitro. Genes Cells. 2002 Jan;7(1):59-73. PMID:11856374
- ↑ Blackwell C, Martin KA, Greenall A, Pidoux A, Allshire RC, Whitehall SK. The Schizosaccharomyces pombe HIRA-like protein Hip1 is required for the periodic expression of histone genes and contributes to the function of complex centromeres. Mol Cell Biol. 2004 May;24(10):4309-20. PMID:15121850
- ↑ Greenall A, Williams ES, Martin KA, Palmer JM, Gray J, Liu C, Whitehall SK. Hip3 interacts with the HIRA proteins Hip1 and Slm9 and is required for transcriptional silencing and accurate chromosome segregation. J Biol Chem. 2006 Mar 31;281(13):8732-9. Epub 2006 Jan 22. PMID:16428807 doi:http://dx.doi.org/M512170200
- ↑ Malay AD, Umehara T, Matsubara-Malay K, Padmanabhan B, Yokoyama S. Crystal structures of fission yeast histone chaperone Asf1 complexed with the Hip1 B-domain or the Cac2 C terminus. J Biol Chem. 2008 May 16;283(20):14022-31. Epub 2008 Mar 11. PMID:18334479 doi:10.1074/jbc.M800594200
