| Structural highlights
Function
H2AZ_YEAST Variant histone H2A which can replace H2A in some nucleosomes. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. This variant is enriched at promoters, it may keep them in a repressed state until the appropriate activation signal is received (PubMed:11000274, PubMed:11081628, PubMed:11090616, PubMed:11509669, PubMed:12628191, PubMed:14645854, PubMed:14690608, PubMed:15045029, PubMed:16239142, PubMed:16344463, PubMed:16543223). Near telomeres, it may counteract gene silencing caused by the spread of heterochromatin proteins (PubMed:16543222). Required for the RNA polymerase II and SPT15/TBP recruitment to the target genes (PubMed:11509669). Involved in chromosome stability (PubMed:15353583). Required to target MPS3 to the inner membrane of the nuclear envelope (PubMed:21518795).[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] H2B1_YEAST Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.[15] [16] [17] [18] [19] [20] [21] [22] [23]
Publication Abstract from PubMed
Chz1 is a specific chaperone for the histone variant H2A.Z in budding yeast. The ternary complex formed by Chz1 and H2A.Z-H2B dimer is the major in vivo substrate of Swi2/snif2-related 1 (SWR1), the ATP-dependent chromatin remodeling enzyme that deposits H2A.Z into chromatin. However, the structural basis for the binding preference of Chz1 for H2A.Z over H2A and the mechanism by which Chz1 modulates the histone replacement remain elusive. Here, we show that Chz1 utilizes 2 distinct structural domains to engage the H2A.Z-H2B dimer for optimal and specific recognition of H2A.Z. The middle region of Chz1 (Chz1-M) directly interacts with 2 highly conserved H2A.Z-specific residues (Gly98 and Ala57) and dictates a modest preference for H2A.Z-H2B. In addition, structural and biochemical analysis show that the C-terminal region of Chz1 (Chz1-C) harbors a conserved DEF/Y motif, which reflects the consecutive D/E residues followed by a single aromatic residue, to engage an arginine finger and a hydrophobic pocket in H2A.Z-H2B, enhancing the binding preference for H2A.Z-H2B. Furthermore, Chz1 facilitates SWR1-mediated H2A.Z deposition by alleviating inhibition caused by aggregation of excess free histones, providing insights into how Chz1 controls the bioavailability of H2A.Z to assist SWR1 in promoter-specific installation of a histone mark. Our study elucidates a novel H2A.Z-recognition mechanism and uncovers a molecular rationale for binding of free histone by specialized histone chaperones in vivo.
Structural insights into histone chaperone Chz1-mediated H2A.Z recognition and histone replacement.,Wang Y, Liu S, Sun L, Xu N, Shan S, Wu F, Liang X, Huang Y, Luk E, Wu C, Zhou Z PLoS Biol. 2019 May 20;17(5):e3000277. doi: 10.1371/journal.pbio.3000277., eCollection 2019 May. PMID:31107867[24]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Jackson JD, Gorovsky MA. Histone H2A.Z has a conserved function that is distinct from that of the major H2A sequence variants. Nucleic Acids Res. 2000 Oct 1;28(19):3811-6. PMID:11000274
- ↑ Santisteban MS, Kalashnikova T, Smith MM. Histone H2A.Z regulats transcription and is partially redundant with nucleosome remodeling complexes. Cell. 2000 Oct 27;103(3):411-22. PMID:11081628
- ↑ Dhillon N, Kamakaka RT. A histone variant, Htz1p, and a Sir1p-like protein, Esc2p, mediate silencing at HMR. Mol Cell. 2000 Oct;6(4):769-80. PMID:11090616
- ↑ Adam M, Robert F, Larochelle M, Gaudreau L. H2A.Z is required for global chromatin integrity and for recruitment of RNA polymerase II under specific conditions. Mol Cell Biol. 2001 Sep;21(18):6270-9. doi: 10.1128/MCB.21.18.6270-6279.2001. PMID:11509669 doi:https://dx.doi.org/10.1128/MCB.21.18.6270-6279.2001
- ↑ Meneghini MD, Wu M, Madhani HD. Conserved histone variant H2A.Z protects euchromatin from the ectopic spread of silent heterochromatin. Cell. 2003 Mar 7;112(5):725-36. doi: 10.1016/s0092-8674(03)00123-5. PMID:12628191 doi:https://dx.doi.org/10.1016/s0092-8674(03)00123-5
- ↑ Mizuguchi G, Shen X, Landry J, Wu WH, Sen S, Wu C. ATP-driven exchange of histone H2AZ variant catalyzed by SWR1 chromatin remodeling complex. Science. 2004 Jan 16;303(5656):343-8. Epub 2003 Nov 26. PMID:14645854 doi:10.1126/science.1090701
- ↑ Krogan NJ, Keogh MC, Datta N, Sawa C, Ryan OW, Ding H, Haw RA, Pootoolal J, Tong A, Canadien V, Richards DP, Wu X, Emili A, Hughes TR, Buratowski S, Greenblatt JF. A Snf2 family ATPase complex required for recruitment of the histone H2A variant Htz1. Mol Cell. 2003 Dec;12(6):1565-76. PMID:14690608
- ↑ Kobor MS, Venkatasubrahmanyam S, Meneghini MD, Gin JW, Jennings JL, Link AJ, Madhani HD, Rine J. A protein complex containing the conserved Swi2/Snf2-related ATPase Swr1p deposits histone variant H2A.Z into euchromatin. PLoS Biol. 2004 May;2(5):E131. Epub 2004 Mar 23. PMID:15045029 doi:10.1371/journal.pbio.0020131
- ↑ Krogan NJ, Baetz K, Keogh MC, Datta N, Sawa C, Kwok TC, Thompson NJ, Davey MG, Pootoolal J, Hughes TR, Emili A, Buratowski S, Hieter P, Greenblatt JF. Regulation of chromosome stability by the histone H2A variant Htz1, the Swr1 chromatin remodeling complex, and the histone acetyltransferase NuA4. Proc Natl Acad Sci U S A. 2004 Sep 14;101(37):13513-8. Epub 2004 Sep 7. PMID:15353583 doi:https://dx.doi.org/10.1073/pnas.0405753101
- ↑ Raisner RM, Hartley PD, Meneghini MD, Bao MZ, Liu CL, Schreiber SL, Rando OJ, Madhani HD. Histone variant H2A.Z marks the 5' ends of both active and inactive genes in euchromatin. Cell. 2005 Oct 21;123(2):233-48. doi: 10.1016/j.cell.2005.10.002. PMID:16239142 doi:https://dx.doi.org/10.1016/j.cell.2005.10.002
- ↑ Li B, Pattenden SG, Lee D, Gutierrez J, Chen J, Seidel C, Gerton J, Workman JL. Preferential occupancy of histone variant H2AZ at inactive promoters influences local histone modifications and chromatin remodeling. Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18385-90. doi: , 10.1073/pnas.0507975102. Epub 2005 Dec 12. PMID:16344463 doi:https://dx.doi.org/10.1073/pnas.0507975102
- ↑ Babiarz JE, Halley JE, Rine J. Telomeric heterochromatin boundaries require NuA4-dependent acetylation of histone variant H2A.Z in Saccharomyces cerevisiae. Genes Dev. 2006 Mar 15;20(6):700-10. PMID:16543222 doi:https://dx.doi.org/10.1101/gad.1386306
- ↑ Millar CB, Xu F, Zhang K, Grunstein M. Acetylation of H2AZ Lys 14 is associated with genome-wide gene activity in yeast. Genes Dev. 2006 Mar 15;20(6):711-22. PMID:16543223 doi:https://dx.doi.org/20/6/711
- ↑ Gardner JM, Smoyer CJ, Stensrud ES, Alexander R, Gogol M, Wiegraebe W, Jaspersen SL. Targeting of the SUN protein Mps3 to the inner nuclear membrane by the histone variant H2A.Z. J Cell Biol. 2011 May 2;193(3):489-507. doi: 10.1083/jcb.201011017. Epub 2011 Apr , 25. PMID:21518795 doi:https://dx.doi.org/10.1083/jcb.201011017
- ↑ Martini EM, Keeney S, Osley MA. A role for histone H2B during repair of UV-induced DNA damage in Saccharomyces cerevisiae. Genetics. 2002 Apr;160(4):1375-87. PMID:11973294
- ↑ Briggs SD, Xiao T, Sun ZW, Caldwell JA, Shabanowitz J, Hunt DF, Allis CD, Strahl BD. Gene silencing: trans-histone regulatory pathway in chromatin. Nature. 2002 Aug 1;418(6897):498. Epub 2002 Jul 14. PMID:12152067 doi:10.1038/nature00970
- ↑ Kao CF, Hillyer C, Tsukuda T, Henry K, Berger S, Osley MA. Rad6 plays a role in transcriptional activation through ubiquitylation of histone H2B. Genes Dev. 2004 Jan 15;18(2):184-95. PMID:14752010 doi:10.1101/gad.1149604
- ↑ Yamashita K, Shinohara M, Shinohara A. Rad6-Bre1-mediated histone H2B ubiquitylation modulates the formation of double-strand breaks during meiosis. Proc Natl Acad Sci U S A. 2004 Aug 3;101(31):11380-5. Epub 2004 Jul 27. PMID:15280549 doi:10.1073/pnas.0400078101
- ↑ Ahn SH, Cheung WL, Hsu JY, Diaz RL, Smith MM, Allis CD. Sterile 20 kinase phosphorylates histone H2B at serine 10 during hydrogen peroxide-induced apoptosis in S. cerevisiae. Cell. 2005 Jan 14;120(1):25-36. PMID:15652479 doi:S009286740401092X
- ↑ Ahn SH, Henderson KA, Keeney S, Allis CD. H2B (Ser10) phosphorylation is induced during apoptosis and meiosis in S. cerevisiae. Cell Cycle. 2005 Jun;4(6):780-3. Epub 2005 Jun 14. PMID:15970663
- ↑ Giannattasio M, Lazzaro F, Plevani P, Muzi-Falconi M. The DNA damage checkpoint response requires histone H2B ubiquitination by Rad6-Bre1 and H3 methylation by Dot1. J Biol Chem. 2005 Mar 18;280(11):9879-86. Epub 2005 Jan 4. PMID:15632126 doi:M414453200
- ↑ Xiao T, Kao CF, Krogan NJ, Sun ZW, Greenblatt JF, Osley MA, Strahl BD. Histone H2B ubiquitylation is associated with elongating RNA polymerase II. Mol Cell Biol. 2005 Jan;25(2):637-51. PMID:15632065 doi:25/2/637
- ↑ Nathan D, Ingvarsdottir K, Sterner DE, Bylebyl GR, Dokmanovic M, Dorsey JA, Whelan KA, Krsmanovic M, Lane WS, Meluh PB, Johnson ES, Berger SL. Histone sumoylation is a negative regulator in Saccharomyces cerevisiae and shows dynamic interplay with positive-acting histone modifications. Genes Dev. 2006 Apr 15;20(8):966-76. Epub 2006 Apr 5. PMID:16598039 doi:gad.1404206
- ↑ Wang Y, Liu S, Sun L, Xu N, Shan S, Wu F, Liang X, Huang Y, Luk E, Wu C, Zhou Z. Structural insights into histone chaperone Chz1-mediated H2A.Z recognition and histone replacement. PLoS Biol. 2019 May 20;17(5):e3000277. doi: 10.1371/journal.pbio.3000277., eCollection 2019 May. PMID:31107867 doi:https://dx.doi.org/10.1371/journal.pbio.3000277
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