Non-redundant functions of H2A.Z.1 and H2A.Z.2 in chromosome segregation and cell cycle progression
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ABSTRACT:
PROVIDER: PRJNA723839 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14301573_1.fastq.gz | Fastqsanger.gz | |||
| SRR14301573_2.fastq.gz | Fastqsanger.gz | |||
| SRR14301574_1.fastq.gz | Fastqsanger.gz | |||
| SRR14301574_2.fastq.gz | Fastqsanger.gz | |||
| SRR14301575_1.fastq.gz | Fastqsanger.gz |
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Project description:H2A.Z is a H2A-type histone variant essential for many aspects of cell biology, ranging from gene expression to genome stability. From deuterostomes, H2A.Z evolved into two paralogues, H2A.Z.1 and H2A.Z.2, that differ by only three amino acids and are encoded by different genes (H2AFZ and H2AFV, respectively). Despite the importance of this histone variant in development and cellular homeostasis, very little is known about the individual functions of each paralogue in mammals. Here, we have investigated the distinct roles of the two paralogues in cell cycle regulation and unveiled non-redundant functions for H2A.Z.1 and H2A.Z.2 in cell division. Our findings show that H2A.Z.1 regulates the expression of cell cycle genes such as Myc and Ki-67 and its depletion leads to a G1 arrest and cellular senescence. On the contrary, H2A.Z.2, in a transcription independent manner, is essential for centromere integrity and sister chromatid cohesion regulation, thus playing a key role in chromosome segregation.
2021-07-25 | GSE173113 | GEO
Project description:H2A.Z is a H2A-type histone variant essential for many aspects of cell biology, ranging from gene expression to genome stability. From deuterostomes, H2A.Z evolved into two paralogues, H2A.Z.1 and H2A.Z.2, that differ by only three amino acids and are encoded by different genes (H2AFZ and H2AFV, respectively). Despite the importance of this histone variant in development and cellular homeostasis, very little is known about the individual functions of each paralogue in mammals. Here, we have investigated the distinct roles of the two paralogues in cell cycle regulation and unveiled non-redundant functions for H2A.Z.1 and H2A.Z.2 in cell division. Our findings show that H2A.Z.1 regulates the expression of cell cycle genes such as Myc and Ki-67 and its depletion leads to a G1 arrest and cellular senescence. On the contrary, H2A.Z.2, in a transcription-independent manner, is essential for centromere integrity and sister chromatid cohesion regulation, thus playing a key role in chromosome segregation.
| S-EPMC8567233 | biostudies-literature
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Project description:H2A.Z is a histone H2A variant that contributes to transcriptional regulation, DNA damage response and limits heterochromatin spreading. In Saccharomyces cerevisiae, H2A.Z is deposited by the SWR-C complex, which relies on several histone chaperones including Nap1 and Chz1 to deliver H2A.Z-H2B dimers to SWR-C. However, the mechanisms by which Nap1 and Chz1 cooperate to bind H2A.Z and their contribution to H2A.Z deposition in chromatin is not well understood. Using structural modeling and molecular dynamics simulations, we identify a series of H2A.Z residues that form a chaperone-specific binding surface. Mutation of these residues revealed different surface requirements for Nap1 and Chz1 interaction with H2A.Z. Consistent with this result, we found that loss of Nap1 or Chz1 individually resulted in mild defects in H2A.Z deposition, but that deletion of both Nap1 and Chz1 resulted in a significant reduction of H2A.Z deposition at promoters and led to heterochromatin spreading. Together, our findings reveal unique H2A.Z surface dependences for Nap1 and Chz1 and a redundant role for these chaperones in H2A.Z deposition.
| S-EPMC5589762 | biostudies-literature
Project description:The histone variant H2A.Z has been implicated in nucleosome exchange, transcriptional activation and Polycomb repression. However, the relationships among these seemingly disparate functions remain obscure. We mapped H2A.Z genome-wide in mammalian ES cells and neural progenitors. H2A.Z is deposited promiscuously at promoters and enhancers, and correlates strongly with H3K4 methylation. Accordingly, H2A.Z is present at poised promoters with bivalent chromatin and at active promoters with H3K4 methylation, but is absent from stably repressed promoters that are specifically enriched for H3K27 trimethylation. We also characterized post-translational modification states of H2A.Z, including a novel species dually-modified by ubiquitination and acetylation that is enriched at bivalent chromatin. Our findings associate H2A.Z with functionally distinct genomic elements, and suggest that post-translational modifications may reconcile its contrasting locations and roles. Examination of histone variant, histone modifications and transcription machinery in 3 cell types
2012-07-19 | E-GEOD-39237 | biostudies-arrayexpress
Project description:Two functionally important DNA sequence elements in centromeres of the fission yeast Schizosaccharomyces pombe are the centromeric central core and the K-type repeat. Both of these DNA elements show internal functional redundancy that is not correlated with a conserved DNA sequence. Specific, but degenerate, sequences in these elements are bound in vitro by the S. pombe DNA-binding proteins Abp1p (also called Cbp1p) and Cbhp, which are related to the mammalian centromere DNA-binding protein CENP-B. In this study, we determined that Abp1p binds to at least one of its target sequences within S. pombe centromere II central core (cc2) DNA with an affinity (K(s) = 7 x 10(9) M(-1)) higher than those of other known centromere DNA-binding proteins for their cognate targets. In vivo, epitope-tagged Cbhp associated with centromeric K repeat chromatin, as well as with noncentromeric regions. Like abp1(+)/cbp1(+), we found that cbh(+) is not essential in fission yeast, but a strain carrying deletions of both genes (Deltaabp1 Deltacbh) is extremely compromised in growth rate and morphology and missegregates chromosomes at very high frequency. The synergism between the two null mutations suggests that these proteins perform redundant functions in S. pombe chromosome segregation. In vitro assays with cell extracts with these proteins depleted allowed the specific assignments of several binding sites for them within cc2 and the K-type repeat. Redundancy observed at the centromere DNA level appears to be reflected at the protein level, as no single member of the CENP-B-related protein family is essential for proper chromosome segregation in fission yeast. The relevance of these findings to mammalian centromeres is discussed.
| S-EPMC85508 | biostudies-literature
Project description:While it has been clearly established that well positioned H2A.Z-containing nucleosomes flank the nucleosome depleted region (NDR) at the transcriptional start site (TSS) of active mammalian genes 1,2, how this chromatin-based information is transmitted through the cell cycle is unknown. We show here that in trophoblast stem (TS) cells, the level of H2A.Z at promoters decreases during S phase coinciding with homotypic (H2A.Z/H2A.Z) nucleosomes flanking the TSS becoming heterotypic (H2A.Z/H2A). Surprisingly, these nucleosomes remain heterotypic at M phase. At the TSS, we identify an unstable heterotypic H2A.Z-containing nucleosome in G1 which, strikingly, is lost following DNA replication. These dynamic changes in H2A.Z at the TSS mirror a global expansion of the NDR at S and M which, unexpectedly, is unrelated to transcriptional activity. Coincident with the loss of H2A.Z at promoters, it is targeted to the centromere when mitosis begins. We surveyed whole genome expression using microarrays, in combination with H2A.Z ChIP-Seq (Illumina) data, to study the H2A.Z distribution on promoters of coding genes in different stages of the cell cycle in Trophoblast Stem (TS) cells. These data are published in Nekrasov et al., H2AZ inheritance during the cell cycle and it's impact on promoter organization and dynamics, Nature Structural and Molecular Biology (in press: accepted for publication on 24 Sep 2012). Mouse Trophoblast stem (TS) cells were grown in cell culture medium. By adding specific drugs cells were arrested at particular stages of the cell cycle: G1; S and M. Total RNA was extracted from TS cells arrested at G1; S and M stages of cell cycle using TRizol (Invitrogen) extraction protocol and purified further the by RNAeasy Extraction Kit (Qiagen). RNA quality was assesed on Bioanalyzer total RNA chip. RNA samples were reverse transcribed and resulted cDNA samples were subjected to DNA microarray analysis (in triplicate) using the GeneChip Mouse Gene 1.0 ST Array (Affymetrix). Robust Multichip Average (RMA) correction and probe set summaries were obtained using Affymetrix Power Tools software annotation (Affymetrix) based on the mm9 mouse genome. Unless otherwise stated, all subsequent expression analyses (see Supplementary Methods) were performed in the R statistical computing environment (version 2.11.1).
2012-11-23 | E-GEOD-41370 | biostudies-arrayexpress
Project description:Comparison of occupancy profiling of Xap5 and H2A.Z/Pht1 in fission yeast. Agilent 60mer array was used to analyze DNA recovered by chromatin immunoprecipitation of Xap5 from fission yeast culture.
2014-07-01 | E-GEOD-46505 | biostudies-arrayexpress