DNA replication-mediated error correction of ectopic CENP-A deposition maintains centromere identity
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ABSTRACT:
PROVIDER: PRJNA436748 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6800120_1.fastq.gz | Fastqsanger.gz | |||
| SRR6800120_2.fastq.gz | Fastqsanger.gz | |||
| SRR6800121_1.fastq.gz | Fastqsanger.gz | |||
| SRR6800121_2.fastq.gz | Fastqsanger.gz | |||
| SRR6800122_1.fastq.gz | Fastqsanger.gz |
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Project description:Chromatin assembled with histone H3 variant CENP-A is the heritable epigenetic determinant of human centromere identity. Using genome-wide mapping and reference models for 23 human centromeres, CENP-A is shown in early G1 to be assembled into nucleosomes within megabase, repetitive a-satellite DNAs at each centromere and onto 11,390 sites on the chromosome arms. Centromere-bound CENP-A is found to be quantitatively maintained during DNA replication by coordinated action of the MCM2 helicase, CAF1, HJURP, and the CCAN network of constitutive centromere components. CCAN serves to tether CENP-A removed by MCM2, thereby enabling local reassembly onto both daughter centromeres with identical DNA sequence preferences and nucleosome phasing as the loading in G1 and independent of CENP-B. Conversely, without CCAN-mediated tethering, DNA replication removes CENP-A from sites on the chromosome arms. Our data identify an MCM2/CAF1/HJURP- and CCAN-dependent error correction mechanism that acts in S-phase to maintain CENP-A-dependent centromere identity.
2019-03-20 | GSE111381 | GEO
Project description:CENP-A is the histone H3 variant necessary to specify the location of all eukaryoticcentromeres via its CENP-A targeting domain and either one of its terminal regions. In humans, several post-translational modifications occur on CENP-A, but their role in centromere function remains controversial. One of these modifications of CENP-A, phosphorylation on serine 7,has been proposed to control centromere assembly and function. Here, using gene targeting at both endogenous CENP-A alleles and gene replacement in human cells, we demonstrate that a CENP-A variant that cannot be phosphorylated at serine 7 maintains correct CENP-C recruitment, faithful chromosome segregation and long-term cell viability. Thus, we conclude that phosphorylation of CENP-A on serine 7 is dispensable to maintain correct centromere dynamics and function.
2019-01-28 | PXD012163 | Pride
Project description:The centromere is the location on each chromosome that directs the assembly of the kinetochore. The underlying hallmark of centromeres in most eukaryotes is the presence of specialised nucleosomes in which canonical histone H3 is replaced by the histone H3 variant CENP-A. The molecular events that mediate a programme to install CENP-A in place of histone H3, at centromeres and how the centromeric chromatin is reorganised for CENP-A assembly during cell cycle remain poorly characterised. Histone H2A variant, H2A.Z is linked to transcriptional competence, in maintaining heterochromatin silencing and enriched in CENP-A chromatin. Our analyses demonstrate that H2A.ZPht1 and the Swr1 complex are associated with CENP-ACnp1 chromatin in fission yeast. Swr1 and Msc1 regulate H2A.ZPht1 deposition at centromeres and along with H2A.ZPht1 maintain CENP-ACnp1 chromatin integrity. Additionally, they coordinate the deposition of CENP-ACnp1 through the cell cycle, coupled with eviction of histone H3 from centromeres. Based on our results, we propose that the centromere is programmed to the widespread incorporation of H2A.ZPht1 via Swr1, and that H2A.ZPht1 dynamics likely play a role in regulating centromeric chromatin by influencing CENP-A incorporation.
2020-12-01 | GSE106585 | GEO
Project description:CENP-A is a centromere-specific histone 3 variant essential for centromere specification. CENP-A partially replaces canonical histone H3 at the centromeres. How the particular CENP-A/H3 ratio at centromeres is precisely maintained is unknown. It also remains unclear how CENP-A is excluded from non-centromeric chromatin. Here we identify Ccp1, an uncharacterized NAP family protein in fission yeast that antagonizes CENP-A loading at both centromeric and non-centromeric regions. Like the CENP-A loading factor HJURP, Ccp1 interacts with CENP-A, and is recruited to centromeres at the end of mitosis in a Mis16-dependent manner. These data indicate that factors with opposing CENP-A loading activities are recruited to centromeres. Furthermore, Ccp1 also cooperates with H2A.Z to evict CENP-A assembled in euchromatin. Structural analyses indicate that Ccp1 forms a homodimer that is required for its anti-CENP-A loading activity. Our study establishes mechanisms for maintenance of CENP-A homeostasis at centromeres and the prevention of ectopic assembly of centromeres.
2016-08-04 | GSE85166 | GEO
Project description:We report the high-throughput profiling of histone variant CNEP-A/Cnp1 in fission yeast Schizosaccharomyces pombe. By obtaining 1-10 ng immunoprecipitated DNA, we generated genome-wide CENP-A/Cnp1 maps of the wild type meiotic haploid progeny of heterozygous deletion diploid wip1∆/+, mhf1∆/+ and mhf2∆/+ and CENP-A/Cnp1 maps of mhf2+ carrying the inactivated Centromere 1 or Centromere 2. We find that CENP-A/Cnp1 spreading into the pericentromeric regions in wild type meiotic progeny of heterozygous deletion diploid wip1∆/+, mhf1∆/+ and mhf2∆/+.
2019-09-28 | GSE131223 | GEO
Project description:CENP-A is a centromere-specific histone 3 variant essential for centromere specification. CENP-A partially replaces canonical histone H3 at the centromeres. How the particular CENP-A/H3 ratio at centromeres is precisely maintained is unknown. It also remains unclear how CENP-A is excluded from non-centromeric chromatin. Here we identify Ccp1, an uncharacterized NAP family protein in fission yeast that antagonizes CENP-A loading at both centromeric and non-centromeric regions. Like the CENP-A loading factor HJURP, Ccp1 interacts with CENP-A, and is recruited to centromeres at the end of mitosis in a Mis16-dependent manner. These data indicate that factors with opposing CENP-A loading activities are recruited to centromeres. Furthermore, Ccp1 also cooperates with H2A.Z to evict CENP-A assembled in euchromatin. Structural analyses indicate that Ccp1 forms a homodimer that is required for its anti-CENP-A loading activity. Our study establishes mechanisms for maintenance of CENP-A homeostasis at centromeres and the prevention of ectopic assembly of centromeres. Examination of cnp1 distribution in one wild type (wt) and two ccp1 mutants.
2016-08-04 | E-GEOD-85166 | biostudies-arrayexpress
Project description:We report the high-throughput profiling of histone modification (H3K9me2) or histone variant CNEP-A/Cnp1 in fission yeast Schizosaccharomyces pombe. By obtaining 1-10 ng immunoprecipitated DNA, we generated genome-wide H3K9me2 or CENP-A/Cnp1 maps of both mhf2∆ and mhf2+ carrying the inactivated Centromere 1 or Centromere 2 in fission yeast. We find that neocemtromeres are formed preferably at pericentromeric regions in single depletion of CENP-T-W-X-S.
2019-09-28 | GSE117955 | GEO
Project description:In most eukaryotes, the centromere is epigenetically defined by nucleosomes that contain the histone H3 variant centromere protein A (CENP-A). Specific targeting of the CENP-A-loading chaperone to the centromere is vital for stable centromere propagation; however, the existence of ectopic centromeres (neocentromeres) indicates that this chaperone can function in different chromatin environments. The mechanism responsible for accommodating the CENP-A chaperone at novel chromatin regions is poorly understood. Here, we report the identification of transient, immature neocentromeres in Schizosaccharomyces pombe, which show reduced association with the CENP-A chaperone Scm3 attributable to persistence of the histone H2A variant H2A.Z. Following acquisition of adjacent heterochromatin or relocation of the immature neocentromeres to subtelomeric regions, H2A.Z was depleted and Scm3 was replenished, leading to subsequent stabilization of the neocentromeres. These findings provide novel insights into histone variant-mediated epigenetic control of neocentromere establishment. Comparison of chromosomal distributions of centromeric proteins and heterochromatin proteins between the NC survivors and their derivatives.
2013-11-03 | E-GEOD-37094 | biostudies-arrayexpress
Project description:In most eukaryotes, the centromere is epigenetically defined by nucleosomes that contain the histone H3 variant centromere protein A (CENP-A). Specific targeting of the CENP-A-loading chaperone to the centromere is vital for stable centromere propagation; however, the existence of ectopic centromeres (neocentromeres) indicates that this chaperone can function in different chromatin environments. The mechanism responsible for accommodating the CENP-A chaperone at novel chromatin regions is poorly understood. Here, we report the identification of transient, immature neocentromeres in Schizosaccharomyces pombe, which show reduced association with the CENP-A chaperone Scm3 attributable to persistence of the histone H2A variant H2A.Z. Following acquisition of adjacent heterochromatin or relocation of the immature neocentromeres to subtelomeric regions, H2A.Z was depleted and Scm3 was replenished, leading to subsequent stabilization of the neocentromeres. These findings provide novel insights into histone variant-mediated epigenetic control of neocentromere establishment.
2013-11-03 | GSE37094 | GEO
Project description:The centromere specific histone H3 variant CENP-A/CENH3 specifies where the kinetochore is formed in most eukaryotes. Despite tight regulation of CENP-A levels in normal cells, overexpression of CENP-A is a feature shared by various types of solid tumors and results in its mislocalization to non-centromeric DNA. How CENP-A is assembled ectopically and the consequences of this mislocalization remain topics of high interest. Here, we report that in human colon cancer cells, the H3.3 chaperones HIRA and DAXX promote ectopic CENP-A deposition. Moreover, the correct balance between levels of the centromeric chaperone HJURP and CENP-A is essential to preclude ectopic assembly by H3.3 chaperones. In addition, we find that ectopic localization can recruit kinetochore components, and correlates with mitotic defects and DNA damage in G1 phase. Finally, CENP-A occupancy at the 8q24 locus is also correlated with amplification and overexpression of the MYC gene within that locus. Overall, these data provide insights into the causes and consequences of histone variant mislocalization in human cancer cells.
2018-10-10 | GSE120230 | GEO