| 2003 |
The SWR1 complex, with Swr1 (a Swi2/Snf2-related ATPase) as its catalytic core, catalyzes ATP-dependent exchange of nucleosomal histone H2A for H2A.Z in nucleosome arrays. Swr1 is required for deposition of H2A.Z at specific chromosome locations in vivo. |
Biochemical reconstitution of histone exchange activity; in vivo ChIP; genetic analysis in S. cerevisiae |
Science |
High |
14645854
|
| 2005 |
Within the SWR1 complex, Swc2 binds directly to H2A.Z and is essential for its transfer into nucleosomes. Swc6 and Arp6 are required for Swc2 association and nucleosome binding; Swc5 and Yaf9 are required for H2A.Z transfer but not for H2A.Z or nucleosome binding. The C-terminal alpha-helix of H2A.Z is crucial for recognition by SWR1. |
Biochemical dissection of SWR1 subunit interactions; pulldown/co-IP; in vitro histone exchange assay; mutagenesis of H2A.Z C-terminal helix |
Nature structural & molecular biology |
High |
16299513
|
| 2007 |
H2A.Z nucleosomes occupy a single predominant rotational setting and multiple translational settings in the S. cerevisiae genome, flanking nucleosome-free regions at promoters of both active and inactive genes, with transcription factor binding sites rotationally exposed near nucleosome borders. |
Deep sequencing of 322,000 individual H2A.Z-containing nucleosomes (genome-wide nucleosome positioning) |
Nature |
High |
17392789
|
| 2000 |
H2A.Z regulates gene transcription in S. cerevisiae; deletion of H2A.Z strongly increases the requirement for SNF/SWI and SAGA remodeling complexes (synthetic genetic interaction). H2A.Z is preferentially crosslinked to intergenic DNA at PHO5 and GAL1 loci, and this association changes with transcriptional activation, placing H2A.Z in a distinct pathway from SNF/SWI and SAGA for chromatin-based transcriptional regulation. |
Genetic epistasis (synthetic lethality/sick interactions); chromatin immunoprecipitation (ChIP) at specific loci in S. cerevisiae |
Cell |
High |
11081628
|
| 2008 |
H2A.Z occupies promoters of developmentally important genes in mouse ES cells in a manner similar to Polycomb group protein Suz12. H2A.Z and PcG protein occupancy is interdependent at promoters (RNAi depletion of H2A.Z reduces PcG occupancy and vice versa), and H2A.Z is necessary for ES cell differentiation and lineage commitment. |
Genome-wide ChIP-seq; RNAi knockdown with gene expression and differentiation assays in mouse ES cells |
Cell |
High |
18992931
|
| 2007 |
A fraction of mammalian H2A.Z is monoubiquitylated; on the inactive X chromosome the majority of H2A.Z is ubiquitylated. Monoubiquitylation of H2A.Z is mediated by the RING1b E3 ligase of the human Polycomb complex, distinguishing H2A.Z associated with facultative heterochromatin from euchromatin-associated H2A.Z. |
Biochemical fractionation; co-immunoprecipitation; immunofluorescence; identification of RING1b as the E3 ligase |
Molecular and cellular biology |
Medium |
17636032
|
| 2008 |
DNA methylation and H2A.Z deposition are mutually antagonistic in Arabidopsis: regions of DNA methylation are quantitatively deficient in H2A.Z. Mutation of MET1 DNA methyltransferase causes losses of H2A.Z at sites gaining methylation and gains of H2A.Z at sites losing methylation; mutation of PIE1 (SWR1 complex subunit) leads to genome-wide hypermethylation. This demonstrates that DNA methylation excludes H2A.Z and H2A.Z protects genes from DNA methylation. |
ChIP-chip; genetic analysis of met1 and pie1 mutants with genome-wide methylation and H2A.Z profiling in Arabidopsis |
Nature |
High |
18815594
|
| 2009 |
H2A.Z incorporation into promoter chromatin of estrogen receptor (ERα) target genes occurs upon gene induction in a cyclic pattern, mediated by the p400 complex. Cellular depletion of H2A.Z or p400 causes severe defects in estrogen signaling and estrogen-specific cell proliferation. H2A.Z incorporation allows nucleosomes to adopt preferential translational positions at the TFF1 promoter and is essential for estrogen-responsive enhancer function. |
ChIP-seq; RNAi knockdown; gene expression analysis; nucleosome positioning assay in human cells |
Genes & development |
High |
19515975
|
| 2009 |
H2A.Z loaded at 5' ends of genes by the Swr1 complex containing a JmjC domain protein mediates suppression of antisense transcripts in fission yeast. H2A.Z is partially redundant with the Clr4-containing heterochromatin complex and RNAi component Ago1 in suppressing antisense transcripts that are normally degraded by the exosome. |
Genetic epistasis (H2A.Z/Clr4/Ago1 double and triple mutant analysis); ChIP; RNA analysis in S. pombe |
Nature |
High |
19693008
|
| 2009 |
H2A.Z deposition in fission yeast requires a novel JmjC domain protein Msc1 as a component of the Swr1 complex. Loss of Msc1, Swr1, or H2A.Z results in loss of centromere silencing and defective chromosome segregation. H2A.Z is required for expression of the centromere protein CENP-C, and overexpression of CENP-C rescues centromere silencing defects associated with H2A.Z loss. |
Genetic analysis; ChIP; epistasis rescue experiments in S. pombe |
The Journal of biological chemistry |
Medium |
19910462
|
| 2013 |
SETD6 lysine methyltransferase monomethylates H2A.Z at lysine 7 (H2AZK7me1). This modification increases upon differentiation of mouse embryonic stem cells; H2AZK7me1 and H3K27me3 co-occupy transcription start sites of differentiation marker genes. Depletion of Setd6 leads to cellular differentiation and compromised self-renewal in mESCs. |
In vitro methyltransferase assay; mass spectrometry; ChIP; siRNA knockdown in mESCs |
Epigenetics |
Medium |
23324626
|
| 2015 |
H2A.Z.2 (encoded by H2AFV) interacts with BRD2 bromodomain protein. H2A.Z.2 controls transcriptional output of E2F target genes in melanoma; BRD2 binding to H2A.Z.2-regulated genes is dependent on H2A.Z.2 levels. H2A.Z.2 deficiency sensitizes melanoma cells to chemotherapy and targeted therapies. |
Co-immunoprecipitation; ChIP-seq; RNAi knockdown; integrated genomic analyses in melanoma cells |
Molecular cell |
Medium |
26051178
|
| 2015 |
H2A.Z in human cells is rapidly removed from chromatin flanking DNA damage by the INO80 remodeling complex. The histone chaperone ANP32E also promotes homologous recombination and works in the same pathway as INO80 for H2A.Z removal. The HR defect in INO80- or ANP32E-depleted cells is rescued by co-depletion of H2A.Z, demonstrating that H2A.Z removal from chromatin is the primary function of INO80 and ANP32E in promoting HR. |
ChIP; epistasis rescue (co-depletion); siRNA knockdown; HR reporter assay in human cells |
EMBO reports |
High |
26142279
|
| 2016 |
The crystal structure of Drosophila YL1 (Swc2) H2A.Z-binding domain (dYL1-Z) in complex with H2A.Z-H2B dimer at 1.9-Å resolution reveals a whip-like structure that wraps over H2A.Z-H2B. Preferential recognition is conferred by three residues in loop 2, the hyperacidic patch, and the extended αC helix of H2A.Z. This domain is essential for H2A.Z deposition in vivo and SRCAP(SWR1)-catalyzed replacement in vitro. |
Crystal structure (1.9 Å); in vitro histone replacement assay; in vivo deposition assay; mutagenesis |
Nature structural & molecular biology |
High |
26974124
|
| 2016 |
YL1 is a specific H2A.Z-deposition chaperone in metazoans. Crystal structure at 2.7 Å of the human YL1-H2A.Z-H2B complex shows YL1 binding triggers extension of the H2A.Z αC helix and contacts the extended acidic patch and entire DNA-binding surface of H2A.Z-H2B. Only four amino acid substitutions in H2A are sufficient to create an H2A.Z-like interface recognized by YL1. |
Crystal structure (2.7 Å); biochemical binding assays; mutagenesis |
Nature structural & molecular biology |
High |
26974126
|
| 2016 |
SMYD3 methyltransferase dimethylates H2A.Z.1 at lysine 101 (H2A.Z.1K101me2), which increases H2A.Z.1 stability by preventing binding to the removal chaperone ANP32E and facilitating interaction with histone H3. SMYD3 and H2A.Z.1K101me2 co-localize at the cyclin A1 promoter, activating its expression and G1-S progression. |
In vitro methyltransferase assay; co-immunoprecipitation; ChIP; cyclin A1 rescue in mouse model; microarray |
Cancer research |
Medium |
27569210
|
| 2016 |
H2A.Z.1 monoubiquitylation (H2A.Z.1ub) at PRC1 target residues is required to maintain Polycomb binding and repress bivalent genes in mESCs. Loss of monoubiquitylation (K3R3 mutant) leads to de-repression of bivalent genes and faulty lineage commitment. Tandem bromodomain protein BRD2 is enriched in H2A.Z.1 chromatin and is gained at de-repressed promoters in H2A.Z.1(K3R3) mESCs; BRD2 inhibition restores gene silencing, revealing an antagonistic relationship between H2A.Z.1ub and BRD2. |
Mutagenesis (H2A.Z.1K3R3); ChIP; quantitative proteomics; BRD2 inhibition rescue experiment in mESCs |
Cell reports |
High |
26804911
|
| 2017 |
Unlike other chromatin remodelers that translocate at the H3-H4 interface, INO80 translocates along DNA at the H2A-H2B interface of nucleosomes and persistently displaces DNA from H2A-H2B, generating DNA torsional strain near the entry site. This unique translocation mechanism drives both nucleosome mobilization and selective exchange of H2A.Z-H2B dimers for H2A-H2B without additional histone chaperones. INO80 translocates and mobilizes H2A.Z-containing nucleosomes more efficiently than H2A-containing nucleosomes. |
Biochemical translocation assays; single-molecule analysis; histone exchange assays in vitro; mutant analysis |
Nature communications |
High |
28604691
|
| 2017 |
PWWP2A is a novel H2A.Z-nucleosome binding protein identified by H2A.Z interactome analysis. PWWP2A binds H2A.Z-containing nucleosomes via multivalent interaction (two internal regions for H2A.Z-specificity/nucleosome contact, PWWP domain for DNA binding). The C-terminal tail of H2A.Z mediates PWWP2A recruitment. PWWP2A depletion impairs cell proliferation via mitotic delay and causes neural crest cell defects in Xenopus. |
Co-immunoprecipitation interactome; domain mapping; genome-wide ChIP-seq; siRNA knockdown; Xenopus knockdown |
The EMBO journal |
Medium |
28645917
|
| 2014 |
H2A.Z is actively exchanged in the hippocampus and cortex in response to fear conditioning. H2A.Z exchange mediates gene expression and restrains formation of recent and remote memory. H2A.Z acts as a negative regulator of hippocampal consolidation and systems consolidation. |
Fear conditioning behavioral paradigm; ChIP; gene expression analysis in mouse hippocampus and cortex |
Nature |
Medium |
25219850
|
| 2019 |
H2A.Z-containing nucleosomes are enriched with H4K20me2 and bound ORC in HeLa cells. H2A.Z-nucleosomes bind directly to SUV420H1, promoting H4K20me2 deposition, which is required for ORC1 binding at replication origins. Depletion of H2A.Z reduces H4K20me2, ORC1 binding, and nascent-strand signals genome-wide, impairing early replication origin licensing and activation. |
In vitro binding assays; ChIP-seq; nascent strand sequencing; H2A.Z depletion in HeLa cells; genome-wide co-localization |
Nature |
High |
31875854
|
| 2023 |
Cryo-EM structure of SUV420H1 bound to H2A.Z-nucleosome reveals direct interaction with H4 N-terminal tail (H4 residues 1-24 forming a lasso-shaped structure projecting H4K20 into the catalytic center), DNA, and nucleosome acidic patch. The SUV420H1 KR loop (residues 214-223) lies close to H2A.Z-specific residues D97/S98 and is crucial for preferential recognition of H2A.Z-nucleosome over canonical H2A-nucleosome. |
Cryo-EM structure; in vitro methyltransferase assay; mutagenesis; in vivo analysis |
Molecular cell |
High |
37536340
|
| 2014 |
The +1 nucleosome is a major barrier to elongating RNAPII for essentially all genes. The extent of this barrier anticorrelates with enrichment of H2A.Z: depletion of H2A.Z from a nucleosome position results in a higher barrier to RNAPII. This shows H2A.Z incorporation at the +1 nucleosome reduces the transcriptional barrier. |
Genome-wide native elongating transcript sequencing (NET-seq) at nucleotide resolution; H2A.Z depletion in yeast |
Molecular cell |
High |
24606920
|
| 2012 |
H2A.Z.2.2, an alternatively spliced variant of H2A.Z, binds to TIP60 and SRCAP chaperone complexes and is actively deposited into chromatin in a replication-independent manner. Its unique C-terminus causes major structural destabilization of nucleosomes as demonstrated by biochemical fractionation, FRAP, size exclusion chromatography, single-molecule FRET, and molecular dynamics simulations. |
Co-immunoprecipitation with TIP60/SRCAP complexes; FRAP; size exclusion chromatography; single-molecule FRET; molecular dynamics simulations; deletion mutant analysis |
Nucleic acids research |
High |
22467210
|
| 2009 |
Acetylation sites of vertebrate H2A.Z (K4, K7, K11, K13, K15) were identified from chicken erythrocytes. H2A.Z stabilizes the nucleosome core particle (NCP) regardless of its acetylation state. Acetylated H2A.Z variants act synergistically with other acetylated core histones to alter NCP conformation. Heteromorphic NCPs containing both H2A.Z and H2A are slightly destabilized only in the presence of acetylation. |
Mass spectrometry (acetylation site identification); NCP reconstitution with acetylated histones and H2A.Z(K/Q) acetylation mimic mutants; biochemical stability assays |
Biochemistry |
Medium |
19385636
|
| 2019 |
Znhit1, a subunit of the SRCAP complex, incorporates H2A.Z into TSS regions of genes governing Lgr5+ intestinal stem cell fate (Lgr5, Tgfb1, Tgfbr2). Mechanistically, Znhit1 promotes H2A.Z incorporation by controlling phosphorylation of the H2A.Z chaperone YL1, enhancing YL1-H2A.Z interaction. |
Conditional knockout mouse; ChIP-seq; co-immunoprecipitation; phosphorylation analysis; intestinal stem cell functional assays |
Nature communications |
Medium |
30842416
|
| 2018 |
H2A.Z deposition and acetylation by the TRRAP/p400/Tip60 complex (which physically associates with transcription factor RBP-J at Notch-dependent enhancers) is required for tight control of canonical Notch target gene activation. Tip60 acetylates H2A.Z when targeted to RBP-J-bound enhancers, upregulating Notch target genes. Drosophila homologs of Tip60, p400, and H2A.Z modulate Notch signaling in vivo. |
ChIP; co-immunoprecipitation; siRNA knockdown; in vivo Drosophila genetic analysis; gene expression assays |
Nucleic acids research |
Medium |
29986055
|
| 2013 |
KAT2A (GCN5) acetylates H2A.Z.1 at promoters of transactivated genes. The DNA repair complex XPC-RAD23-CEN2 interacts with both H2A.Z and KAT2A, recruiting KAT2A to promoters to license H2A.Z.1 acetylation. KAT2A selectively acetylates H2A.Z.1 but not H2A.Z.2 in vitro; alanine-14 in H2A.Z.2 inhibits KAT2A activity. Acetyl-H2A.Z.1 recruits BRD2 to promote RNAPII recruitment. |
In vitro acetyltransferase assay; co-immunoprecipitation; ChIP; mutagenesis (non-acetylable H2A.Z.1); RNAPII recruitment assay |
Nature chemical biology |
High |
31527837
|
| 2022 |
TIP60 (KAT5) is essential for acetylation of H2A.Z specifically at lysine 7 in human and mouse cells. Loss of TIP60 causes complete cell growth arrest with failure of chromosome alignment during mitosis. This growth arrest is independent of p53, INK4A, and ARF tumor suppressors. |
Inducible Cre-recombinase and CRISPR/Cas9 deletion of TIP60; ChIP; RNA-seq; cell cycle analysis; live imaging of mitosis |
Cell death & disease |
Medium |
35853868
|
| 2022 |
Tip60 acetyltransferase acetylates H2A.Z, and loss of H2A.Z acetylation interferes with H3K4me3 deposition and activation of bivalent, lineage-restricted genes during neuronal fate specification. H2A.Z acetylation does not affect chromatin accessibility but is required for epigenetic competence (bivalent chromatin activation) during cell lineage transition. |
Proteomics; genetic depletion of Tip60; ChIP-seq; ATAC-seq; RNA-seq; neuronal differentiation assays |
Molecular cell |
Medium |
36417913
|
| 2020 |
H2A.Z nucleosomes are more enriched in unwrapped states compared with canonical nucleosomes in mouse ES cells, as measured by MNase-X-ChIP-seq. Depletion of H2A.Z results in decreased unwrapping of H3.3 nucleosomes and increased CTCF binding, demonstrating that H2A.Z regulates nucleosome unwrapping in vivo and that its transcriptional and CTCF-regulatory functions correlate with nucleosome unwrapping states. |
MNase-X-ChIP-seq; re-ChIP; CTCF CUT&RUN; H2A.Z depletion in mouse ES cells |
Nucleic acids research |
Medium |
32392318
|
| 2021 |
Cryo-EM structures of H2A.Z-containing nucleosomes and chromatin fibers show that H2A.Z incorporation increases mobility of DNA termini in nucleosomes (due to its shorter C-terminus) while simultaneously enabling nucleosome arrays to form a more regular and condensed chromatin fiber. This structural basis provides a mechanistic explanation for H2A.Z's dual activating and repressive transcriptional roles. |
Cryo-EM structure of nucleosome and chromatin fiber; deletion mutant analysis of H2A.Z C-terminus |
Nucleic acids research |
High |
34643712
|
| 2020 |
Cryo-EM structure of H2A.Z.2.2-containing nucleosome (Z.2.2-NCP) shows it compacts ~125 bp of DNA (less than canonical ~147 bp). Nineteen H2A.Z.2.2-specific residues including a ROF ('regulating-octamer-folding') sequence are responsible for nucleosome opening and also required for SWR1-dependent histone replacement. |
Cryo-EM structure; MNase digestion assay; mutagenesis of ROF sequence; SWR1-dependent replacement assay |
The EMBO journal |
High |
33073403
|
| 2022 |
Single-molecule FRET analysis of SWR1-mediated H2A.Z deposition reveals three ATP-dependent phases: (1) a priming step involving transient DNA unwrapping and histone octamer deformations; (2) rapid loss of H2A-H2B; (3) release of displaced H2A-H2B from the SWR1-nucleosome complex, facilitated by histone chaperones. SWR1 intrinsically senses long-linker DNA to preferentially exchange H2A.Z on the distal face of asymmetrically positioned nucleosomes. |
Three-color single-molecule FRET; ensemble biochemical assays; real-time single nucleosome remodeling imaging |
Science advances |
High |
35263135
|
| 2022 |
SWR1C (yeast SWR1 complex) uses multiple ATP-dependent steps for H2A.Z deposition, identified by single-molecule and ensemble methods: an initial priming step (transient DNA unwrapping and octamer deformations), rapid H2A loss, and subsequent H2A/H2B release from the H2A.Z nucleosomal product. Rates of priming and H2A/H2B dimer release are sensitive to ATP concentration. |
Single-molecule real-time analysis of nucleosome remodeling; ensemble histone exchange assays; ATP concentration titrations |
Nature communications |
High |
36396651
|
| 2019 |
The crystal structure of the Chz1-H2A.Z-H2B ternary complex reveals that Chz1 uses two distinct structural domains: the middle region (Chz1-M) directly interacts with H2A.Z-specific residues Gly98 and Ala57 for modest preferential binding; the C-terminal region (Chz1-C) harbors a DEF/Y motif engaging an arginine finger and hydrophobic pocket in H2A.Z-H2B, enhancing binding preference. Chz1 facilitates SWR1-mediated H2A.Z deposition by controlling bioavailability of free H2A.Z. |
Crystal structure; biochemical binding assays; mutagenesis; in vitro SWR1 histone deposition assay |
PLoS biology |
High |
31107867
|
| 2017 |
Nap1 and Chz1 have redundant roles as histone chaperones for H2A.Z deposition in S. cerevisiae. They use different H2A.Z surface residues for interaction. Loss of either Nap1 or Chz1 alone causes mild H2A.Z deposition defects, but deletion of both results in significant reduction of H2A.Z at promoters and heterochromatin spreading. |
Structural modeling; molecular dynamics simulations; mutagenesis; ChIP; genetic double deletion analysis in S. cerevisiae |
Scientific reports |
Medium |
28883625
|
| 2021 |
H2A.Z.1 and H2A.Z.2 have non-redundant functions in cell division. H2A.Z.1 regulates expression of cell cycle genes (Myc, Ki-67) and its depletion leads to G1 arrest and cellular senescence. H2A.Z.2, in a transcription-independent manner, is essential for centromere integrity and sister chromatid cohesion regulation, playing a key role in chromosome segregation. |
Isoform-specific siRNA depletion; cell cycle analysis; live-cell imaging; ChIP-seq; RNA-seq in human cells |
EMBO reports |
Medium |
34423893
|
| 2021 |
H2A.Z.1 and H2A.Z.2 have specific interactors (identified by mass spectrometry) that can mediate functional antagonism. They can replace each other at transcription start sites and regulate both distinct and overlapping gene sets in a context-dependent manner. The balance between the two isoforms at promoters critically regulates specific gene expression. |
Endogenously-tagged protein immunoprecipitation; mass spectrometry; RNA-seq; ChIP-seq in human cells |
eLife |
Medium |
32109204
|
| 2023 |
SENP5 deSUMOylates H2A.Z, and this modification regulates homologous recombination-mediated DNA damage repair. The SUMOylation balance of H2A.Z modulates HR repair and cancer radioresistance. H2A.Z was identified as a SENP5 deSUMOylation substrate by SUMO-proteomic mass spectrometry and co-immunoprecipitation. |
SUMO-proteomic mass spectrometry; co-immunoprecipitation; HR reporter assay; siRNA knockdown; PDO and PDX models |
Journal of experimental & clinical cancer research |
Medium |
37684630
|
| 2023 |
TORC1 activates the Rpd3L histone deacetylase complex to deacetylate H2A.Z, blocking its deposition into chromatin at autophagy-related gene promoters. Simultaneously, Rpd3L deacetylates the chromatin remodeler Ino80 at K929, stabilizing it and enabling H2A.Z eviction from autophagy genes. This TORC1-Rpd3L-H2A.Z axis represses autophagy-related gene transcription under nutrient-rich conditions. |
Biochemical deacetylase assays; co-immunoprecipitation; ChIP; genetic epistasis; rapamycin treatment in yeast |
Science advances |
Medium |
36888706
|
| 2020 |
VPS72/YL1 mediates H2A.Z deposition required for nuclear reassembly after mitosis. Depletion of VPS72 or H2A.Z by siRNA or in vitro depletion results in malformed and nonfunctional nuclei. VPS72 functions outside of the SRCAP and EP400 remodeling complexes for this specific H2A.Z deposition activity. |
Cell-free nuclear reassembly assay; siRNA knockdown; live-cell imaging; biochemical fractionation |
Cells |
Medium |
32708675
|
| 2017 |
H2A.Z promotes cotranscriptional splicing of suboptimal introns in S. pombe. H2A.Z and Swr1 ATPase are required during temperature stress for efficient splicing of introns with nonconsensus splice sites. Mutating affected splice sites to consensus suppresses the H2A.Z requirement for splicing of that intron. Overexpression of splicing ATPase Prp16 suppresses growth and splicing defects of H2A.Z mutants, placing H2A.Z upstream of Prp16 in a pathway promoting weak intron recognition. |
Epistatic miniarray profiles (EMAP); splicing microarray; splice site mutagenesis; genetic suppression by Prp16 overexpression in S. pombe |
Genes & development |
Medium |
28446597
|
| 2021 |
H2A.Z depletion in terminally differentiated post-mitotic muscle cells in vivo shows that H2A.Z is dispensable for maintaining or activating transcription in the absence of cell division, as shown by ChIP-seq, RNA-seq, and ATAC-seq. H2A.Z enrichment at active promoters is a marker but not a driver of transcription in post-mitotic cells. |
In vivo conditional H2A.Z knockout in post-mitotic muscle; ChIP-seq; RNA-seq; ATAC-seq |
Nucleic acids research |
Medium |
32266374
|
| 2021 |
In Drosophila embryos, H2A.Z enrichment at transcription start sites precedes ZGA and RNA Pol II loading. In vivo knockdown of Domino (H2A.Z chaperone/ATPase) reduces H2A.Z deposition at TSS, causes global downregulation of housekeeping genes at ZGA, and compromises establishment of 3D chromatin structure. |
GRO-seq; HiC; ChIP-seq; in vivo RNAi knockdown in Drosophila embryos |
Nature communications |
Medium |
34853314
|
| 2018 |
H2A.Z promotes meiotic DNA double-strand break formation in fission yeast. In H2A.Z-lacking mutants, multiple proteins involved in DSB formation (including Spo11 homolog and its regulators) show reduced chromatin association, and nuclei are more compact. H2A.Z promotes DSB formation by modulating chromosome architecture to enhance interaction between DSB-related proteins and cohesin-loaded chromatin. |
ChIP; meiotic DSB assay; nuclear architecture analysis; genetic analysis in S. pombe |
Nucleic acids research |
Medium |
29145618
|
| 2018 |
H2A.Z.1 regulates gliogenesis by cooperating with histone chaperone ASF1a to regulate H3K56 acetylation (H3K56ac), which in turn directly affects expression of FOLR1 (folate receptor 1). FOLR1 participates in gliogenesis through the JAK-STAT signaling pathway. |
siRNA knockdown; ChIP; RNA-seq; co-immunoprecipitation with ASF1a; neural precursor cell differentiation assays |
Nucleic acids research |
Medium |
29982651
|
| 2015 |
The DREAM complex (containing C. elegans lin-35/Rb homolog) promotes high gene-body H2A.Z (HTZ-1) levels at target genes. In lin-35 mutants, DREAM targets show reduced gene body H2A.Z and increased expression. Many DREAM targets are also upregulated in htz-1/H2A.Z mutants, indicating that gene body H2A.Z plays a repressive role at DREAM target genes. |
ChIP-seq; genetic epistasis (lin-35 and htz-1 mutants); RNA-seq in C. elegans |
Genes & development |
Medium |
25737279
|
| 2024 |
The role of H2A.Z.1 in memory depends on its acetylation status: acetyl-mimic H2A.Z.1 (K4/7/11Q) improves memory, while acetyl-defective H2A.Z.1 (K4/7/11A) impairs memory. H2A.Z.1KA preferentially affects genes involved in synaptic function. H2A.Z.1 depletion or expression of lysine mutants influences alternative splicing of neuronal genes, revealing that H2A.Z.1 regulates both gene expression and splicing in neurons through post-translational modifications. |
AAV-mediated overexpression of acetyl-mimic and acetyl-defective H2A.Z.1 mutants; fear conditioning behavioral assays; RNA-seq; splicing analysis in mouse hippocampus |
Neuropsychopharmacology |
Medium |
38366138
|
| 2021 |
Somatic mutations in SRCAP complex subunit genes cause defective H2A.Z deposition in uterine leiomyomas. In these tumors, H2A.Z loss at TSS is associated with increased chromatin accessibility and upregulation of bivalent embryonic stem cell genes. Germline mutations in SRCAP members YEATS4 and ZNHIT1 predispose to uterine leiomyoma through epigenetic instability caused by deficient H2A.Z deposition. |
Whole-genome sequencing; ATAC-seq; ChIP-seq; HiChIP; RNA-seq of primary tumor tissues |
Nature |
High |
34349258
|