Chz1, a Nuclear Chaperone for Histone H2AZ

Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Molecular Cell (Impact Factor: 14.46). 03/2007; 25(3):357-68. DOI: 10.1016/j.molcel.2006.12.015
Source: PubMed

ABSTRACT The histone variant H2AZ marks nucleosomes flanking the promoters of most genes of budding yeast. The incorporation of H2AZ into chromatin is dependent on the SWR1 complex, which catalyses the replacement of conventional histone H2A with H2AZ. In cells, the pool of unincorporated histone H2AZ has previously been found in association with Nap1, a chaperone for conventional histone H2A-H2B. Here, we report the discovery of Chz1, a histone chaperone that has preference for H2AZ and can also deliver a source of the histone variant for SWR1-dependent histone replacement. Bacterially expressed Chz1 forms a heterotrimer with H2AZ-H2B, stabilizing the association of the histone dimer. We have identified a conserved motif important for histone variant recognition within the H2AZ-interacting domain of Chz1. The presence of this motif in other metazoan proteins suggests that H2AZ-specific chaperones may be widely conserved.

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    • "Earlier work has shown that the structures of H2A-and H2A.Z-containing nucleosomes show prominent differences in the region C-terminal to the histone-fold domain (Suto et al., 2000). This C-terminal region is important for binding of the free H2A.Z-H2B dimer to specific chaperones (Luk et al., 2007; Zhou et al., 2008; Hong et al., 2014), and for effector interactions postincorporation (Clarkson et al., 1999; Adam et al., 2001). For histone H2A.Z replacement, our analysis shows that SWR1 utilizes other unique and conserved features of the H2A nucleosome for substrate specificity. "
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    ABSTRACT: The histone variant H2A.Z is a universal mark of gene promoters, enhancers and regulatory elements in eukaryotic chromatin. The chromatin remodeler SWR1 mediates site-specific incorporation of H2A.Z by a multi-step histone replacement reaction, evicting histone H2A-H2B from the canonical nucleosome and depositing the H2A.Z-H2B dimer. Binding of both substrates-the canonical nucleosome and the H2A.Z-H2B dimer, is essential for activation of SWR1. We found that SWR1 primarily recognizes key residues within the α2 helix in the histone-fold of nucleosomal histone H2A, a region not previously known to influence remodeler activity. Moreover, SWR1 interacts preferentially with nucleosomal DNA at superhelix location 2 on the nucleosome face distal to its linker-binding site. Our findings provide new molecular insights on recognition of the canonical nucleosome by a chromatin remodeler, and have implications for ATP-driven mechanisms of histone eviction and deposition.
    eLife Sciences 06/2015; 4. DOI:10.7554/eLife.06845 · 8.52 Impact Factor
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    • "These data reveal a level of crosstalk between histone chaperones and histone deacetylation during gene regulation. Chz1 is a histone chaperone that shows a preference for H2AZ– H2B over H2A–H2B and cooperates with the SWR1 complex in the exchange of H2A for Htz1p [17]. The histone chaperone Nap1 can bind H2A–H2B dimers and (H3–H4)2 tetramers with similar high affinity and promotes nucleosome assembly by eliminating nonnucleosomal histone DNA interactions [18]. "
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    ABSTRACT: The histone chaperones play an important role in chromatin assembly and disassembly during replication and transcription. We have assessed the global roles of histone chaperones in Saccharomyces cerevisiae. Microarray transcriptional analyzes indicate that histone chaperones have their own specific target genes, and various histone chaperones have partially overlapping functions during transcriptional regulation. The histone deacetylase inhibitor TSA and histone chaperones Asf1, Vps75 and Rtt106 can function in parallel pathways to regulate transcription. Moreover, TSA can specifically antagonize histone chaperone Chz1-mediated telomere anti-silencing. This study demonstrates that a mutual cross-talk mechanism exists between histone chaperones and histone deacetylation in transcriptional regulation.
    FEBS letters 08/2011; 585(15):2519-25. DOI:10.1016/j.febslet.2011.06.036 · 3.34 Impact Factor
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    • "Whether binding to both the NLS and/or M5 region of Htz1 is required for nuclear translocation is unknown. However, the fact that we can remove the C-terminal tail of Htz1, which is involved in binding to several nuclear proteins (Wu et al., 2005, 2009; Luk et al., 2007), suggests that this region is dispensable . The Nap1 chaperone interacts with the Htz1 NLS region and might bridge its interaction with karyopherins (Straube et al., 2010), yet neither Mps3 binding to Htz1 nor its localization to the INM requires Nap1 or the other Htz1 chaperone Chz1. "
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    ABSTRACT: Understanding the relationship between chromatin and proteins at the nuclear periphery, such as the conserved SUN family of inner nuclear membrane (INM) proteins, is necessary to elucidate how three-dimensional nuclear architecture is established and maintained. We found that the budding yeast SUN protein Mps3 directly binds to the histone variant H2A.Z but not other histones. Biochemical and genetic data indicate that the interaction between Mps3 and H2A.Z requires the Mps3 N-terminal acidic domain and unique sequences in the H2A.Z N terminus and histone-fold domain. Analysis of binding-defective mutants showed that the Mps3-H2A.Z interaction is not essential for any previously described role for either protein in nuclear organization, and multiple lines of evidence suggest that Mps3-H2A.Z binding occurs independently of H2A.Z incorporation into chromatin. We demonstrate that H2A.Z is required to target a soluble Mps3 fragment to the nucleus and to localize full-length Mps3 in the INM, indicating that H2A.Z has a novel chromatin-independent function in INM targeting of SUN proteins.
    The Journal of Cell Biology 05/2011; 193(3):489-507. DOI:10.1083/jcb.201011017 · 9.69 Impact Factor
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