Plasticity and Epigenetic Inheritance of Centromere-specific Histone H3 (CENP-A)-containing Nucleosome Positioning in the Fission Yeast

Yao, Jianhui; Liu, Xingkun; Sakuno, Takeshi; Li, Wenzhu; Xi, Yuanxin; Aravamudhan, Pavithra; Joglekar, Ajit P.; Li, Wei; Watanabe, Yoshinori; He, Xiangwei

doi:10.1074/jbc.m113.471276

Cited by 16 publications

(29 citation statements)

References 57 publications

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“…We previously have shown that cnt2:: ade6 + expression inversely correlates with Cnp1 occupancy on ade6 + . Furthermore, by tracking the colony coloration through cell lineages, we have demonstrated that the state of ade6 + expression, and thereby, Cnp1 occupancy on ade6 + , is inherited through cell generations, but can change abruptly within one generation at low rates [16]. …”

Section: Resultsmentioning

confidence: 99%

Replication stress affects the fidelity of nucleosome-mediated epigenetic inheritance

Li¹,

Yi²,

Agbu³

et al. 2017

PLoS Genet

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The fidelity of epigenetic inheritance or, the precision by which epigenetic information is passed along, is an essential parameter for measuring the effectiveness of the process. How the precision of the process is achieved or modulated, however, remains largely elusive. We have performed quantitative measurement of epigenetic fidelity, using position effect variegation (PEV) in Schizosaccharomyces pombe as readout, to explore whether replication perturbation affects nucleosome-mediated epigenetic inheritance. We show that replication stresses, due to either hydroxyurea treatment or various forms of genetic lesions of the replication machinery, reduce the inheritance accuracy of CENP-A/Cnp1 nucleosome positioning within centromere. Mechanistically, we demonstrate that excessive formation of single-stranded DNA, a common molecular abnormality under these conditions, might have correlation with the reduction in fidelity of centromeric chromatin duplication. Furthermore, we show that replication stress broadly changes chromatin structure at various loci in the genome, such as telomere heterochromatin expanding and mating type locus heterochromatin spreading out of the boundaries. Interestingly, the levels of inheritable expanding at sub-telomeric heterochromatin regions are highly variable among independent cell populations. Finally, we show that HU treatment of the multi-cellular organisms C. elegans and D. melanogaster affects epigenetically programmed development and PEV, illustrating the evolutionary conservation of the phenomenon. Replication stress, in addition to its demonstrated role in genetic instability, promotes variable epigenetic instability throughout the epigenome.

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Section: Resultsmentioning

confidence: 99%

Replication stress affects the fidelity of nucleosome-mediated epigenetic inheritance

Li¹,

Yi²,

Agbu³

et al. 2017

PLoS Genet

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“…Using an experimental procedure, the pedigree analysis, to track the ON and OFF states of the CEN::ade6 reporter through mitotic cell generations at the individual cell level, we have shown that the transcription states of CEN::ade6 are inheritable through cell generations. Switches between the two states are also detected at constant rates (15). CEN-PEV vividly reflects the epigenetic inheritance and the dynamic switching of centromeric chromatin states.…”

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confidence: 85%

“…ade6 or ura4) inserted within the centromeric core region (referred to as CEN-PEV in this work) (26). Subsequent studies, including those from our laboratory, have demonstrated that in CEN-PEV, Cnp1 (CENP-A homolog in fission yeast) nucleosome occupancy on the reporter gene correlates with its transcriptional silencing (15,27,28).…”

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confidence: 88%

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Ccp1 modulates epigenetic stability at centromeres and affects heterochromatin distribution in Schizosaccharomyces pombe

2018

Journal of Biological Chemistry

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Distinct chromatin organization features, such as centromeres and heterochromatin domains, are inherited epigenetically. However, the mechanisms that modulate the accuracy of epigenetic inheritance, especially at the individual nucleosome level, are not well-understood. Here, using ChIP and next-generation sequencing (ChIP-Seq), we characterized Ccp1, a homolog of the histone chaperone Vps75 in budding yeast that functions in centromere chromatin duplication and heterochromatin maintenance in fission yeast (). We show that Ccp1 is enriched at the central core regions of the centromeres. Of note, among all histone chaperones characterized, deletion of the gene uniquely reduced the rate of epigenetic switching, manifested as position effect variegation within the centromeric core region (CEN-PEV). In contrast, gene deletion of other histone chaperones either elevated the PEV switching rates or did not affect centromeric PEV. Ccp1 and the kinetochore components Mis6 and Sim4 were mutually dependent forcentromere or kinetochore association at the proper levels. Moreover, Ccp1 influenced heterochromatin distribution at multiple loci in the genome, including the subtelomeric and the pericentromeric regions. We also found that Gar2, a protein predominantly enriched in the nucleolus, functions similarly to Ccp1 in modulating the epigenetic stability of centromeric regions, although its mechanism remained unclear. Together, our results identify Ccp1 as an important player in modulating epigenetic stability and maintaining proper organization of multiple chromatin domains throughout the fission yeast genome.

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“…culturing are subject to "centromere drift" (Hori, Kagawa et al 2017) similar to the repeat-associated 13 regional centromeres of Schizosaccharomyces pombe that exhibit stochastic repositioning of CENPA 14 within CEN chromatin as a consequence of an oversized centromeric core (Yao, Liu et al 2013). The 15 existence of such plasticity in CEN chromatin indicates that centromeres in vertebrates to the 16 unicellular fission yeast are specified and propagated by sequence independent mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Orc4 spatiotemporally stabilizes centromeric chromatin

Sreekumar

Kumari

Bakshi

et al. 2018

Preprint

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words) 1Spatiotemporal regulation in DNA replication maintains kinetochore stability. The epigenetically 2 regulated centromeres (CENs) in the budding yeast Candida albicans have unique DNA sequences, 3 replicate early and are clustered throughout the cell cycle. In this study, the genome-wide occupancy 4 of replication initiation protein Orc4 reveals its abundance at all CENs in C. albicans. Orc4 associates 5 with four different DNA motifs, one of which coincides with tRNA genes. Hi-C combined with 6 genome-wide replication timing analyses identify enriched interactions among early or late replicating 7Orc4-bound regions. A simulated polymer model of chromosomes reveals that early replicating and 8 strongly enriched Orc4-bound sites localize towards the kinetochores. Orc4 is constitutively localized 9to CENs, and both Orc4 and Mcm2 stabilize CENPA. CENPA chaperone Scm3 localizes at the 10 kinetochore during anaphase, coinciding with the loading time of CENPA. We propose that this 11 spatiotemporal nuclear localization of Orc4, with Mcm2 and Scm3, recruits CENPA and stabilizes 12 centromeric chromatin.

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Plasticity and Epigenetic Inheritance of Centromere-specific Histone H3 (CENP-A)-containing Nucleosome Positioning in the Fission Yeast

Cited by 16 publications

References 57 publications

Replication stress affects the fidelity of nucleosome-mediated epigenetic inheritance

Replication stress affects the fidelity of nucleosome-mediated epigenetic inheritance

Ccp1 modulates epigenetic stability at centromeres and affects heterochromatin distribution in Schizosaccharomyces pombe

Orc4 spatiotemporally stabilizes centromeric chromatin

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