Global analyses of cell cycle dependent changes in fission yeast genome organization reveal correlations with alterations in transcript levels
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ABSTRACT:
ORGANISM(S): Schizosaccharomyces pombe
PROVIDER: GSE52287 | GEO | 2014/11/07
SECONDARY ACCESSION(S): PRJNA227342
REPOSITORIES: GEO
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Project description:The successful progression of a cell through the cell cycle requires the temporal regulation of many biological processes, including gene transcript levels and the number and condensation of chromosomes. Fission yeast (Schizosaccharomyces pombe) is a paradigm for cell cycle research and model for higher eukaryotic cells. Due to the small size of its genome, it is highly amenable to high resolution studies of the spatial organization of its genome. Here we present the results of a high resolution study in which we used synchronised S. pombe cells to investigate cell cycle phase dependent changes in genome organization and transcription patterns. We reveal cell cycle dependant changes in connections within and between chromosomes while confirming previously observed features of genome organization, such as telomere clustering. Our results show that chromosomes are effectively circular throughout the cell cycle and that they remain connected even during the M phase. Determining the structure and transcript levels for matched synchronized cells revealed: 1) that genes with high transcript levels are highly connected with the genome at specific stages of the cell cycle; and 2) that interactions have positive and negative effects on transcript levels. We hypothesize that the observed correlations between transcript levels and the formation and disruption of cell cycle specific chromosomal interactions implicate genome organization in epigenetic inheritance and bookmarking.
2014-11-07 | GSE52283 | GEO
Project description:The successful progression of a cell through the cell cycle requires the temporal regulation of many biological processes, including gene transcript levels and the number and condensation of chromosomes. Fission yeast (Schizosaccharomyces pombe) is a paradigm for cell cycle research and model for higher eukaryotic cells. Due to the small size of its genome, it is highly amenable to high resolution studies of the spatial organization of its genome. Here we present the results of a high resolution study in which we used synchronised S. pombe cells to investigate cell cycle phase dependent changes in genome organization and transcription patterns. We reveal cell cycle dependant changes in connections within and between chromosomes while confirming previously observed features of genome organization, such as telomere clustering. Our results show that chromosomes are effectively circular throughout the cell cycle and that they remain connected even during the M phase. Determining the structure and transcript levels for matched synchronized cells revealed: 1) that genes with high transcript levels are highly connected with the genome at specific stages of the cell cycle; and 2) that interactions have positive and negative effects on transcript levels. We hypothesize that the observed correlations between transcript levels and the formation and disruption of cell cycle specific chromosomal interactions implicate genome organization in epigenetic inheritance and bookmarking.
2014-11-07 | GSE52284 | GEO
Project description:Thymidine analogues are powerful tools when studying DNA synthesis including DNA replication, repair and recombination. However, these analogues have been reported to have severe effects on cell-cycle progression and growth, the very processes being investigated in most of these studies. Here, we have analyzed the effects of 5-ethynyl-2'-deoxyuridine (EdU) and 5-Chloro-2'-deoxyuridine (CldU) using fission yeast cells and optimized the labelling procedure. We find that both analogues affect the cell cycle, but that the effects can be mitigated by using the appropriate analogue, short pulses of labelling and low concentrations. In addition, we report sequential labelling of two consecutive S phases using EdU and 5-bromo-2'-deoxyuridine (BrdU). Furthermore, we show that detection of replicative DNA synthesis is much more sensitive than DNA-measurements by flow cytometry.
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Project description:Eukaryotic genomes are highly ordered through various mechanisms, including topologically associating domain (TAD) organization. We employed an in situ Hi-C approach to follow the 3D organization of the fission yeast genome during the cell cycle. We demonstrate that during mitosis, large domains of 300 kb-1 Mb are formed by condensin. This mitotic domain organization does not suddenly dissolve, but gradually diminishes until the next mitosis. By contrast, small domains of 30-40 kb that are formed by cohesin are relatively stable across the cell cycle. Condensin and cohesin mediate long- and short-range contacts, respectively, by bridging their binding sites, thereby forming the large and small domains. These domains are inversely regulated during the cell cycle but assemble independently. Our study describes the chromosomal oscillation between the formation and decay phases of the large and small domains, and we predict that the condensin-mediated domains serve as chromosomal compaction units.
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Project description:Large RNA-binding complexes play a central role in gene expression and orchestrate production, function, and turnover of mRNAs. The accuracy and dynamics of RNA-protein interactions within these molecular machines are essential for their function and are mediated by RNA-binding proteins (RBPs). Here, we show that fission yeast whole-cell poly(A)+ RNA-protein crosslinking data provide information on the organization of RNA-protein complexes. To evaluate the relative enrichment of cellular RBPs on poly(A)+ RNA, we combine poly(A)+ RNA interactome capture with a whole-cell extract normalization procedure. This approach yields estimates of in vivo RNA-binding activities that identify subunits within multiprotein complexes that directly contact RNA. As validation, we trace RNA interactions of different functional modules of the 3' end processing machinery and reveal additional contacts. Extending our analysis to different mutants of the RNA exosome complex, we explore how substrate channeling through the complex is affected by mutation. Our data highlight the central role of the RNA helicase Mtl1 in regulation of the complex and provide insights into how different components contribute to engagement of the complex with substrate RNA. In addition, we characterize RNA-binding activities of novel RBPs that have been recurrently detected in the RNA interactomes of multiple species. We find that many of these, including cyclophilins and thioredoxins, are substoichiometric RNA interactors in vivo. Because RBPomes show very good overall agreement between species, we propose that the RNA-binding characteristics we observe in fission yeast are likely to apply to related proteins in higher eukaryotes as well.
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Project description:Successful progression through the cell cycle requires spatial and temporal regulation of gene transcript levels and the number, positions and condensation levels of chromosomes. Here we present a high resolution survey of genome interactions in Schizosaccharomyces pombe using synchronized cells to investigate cell cycle dependent changes in genome organization and transcription. Cell cycle dependent interactions were captured between and within S. pombe chromosomes. Known features of genome organization (e.g. the clustering of telomeres and retrotransposon long terminal repeats (LTRs)) were observed throughout the cell cycle. There were clear correlations between transcript levels and chromosomal interactions between genes, consistent with a role for interactions in transcriptional regulation at specific stages of the cell cycle. In silico reconstructions of the chromosome organization within the S. pombe nuclei were made by polymer modeling. These models suggest that groups of genes with high and low, or differentially regulated transcript levels have preferred positions within the S. pombe nucleus. We conclude that the S. pombe nucleus is spatially divided into functional sub-nuclear domains that correlate with gene activity. The observation that chromosomal interactions are maintained even when chromosomes are fully condensed in M phase implicates genome organization in epigenetic inheritance and bookmarking.
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Project description:Eukaryotic genomes are highly ordered through various mechanisms, including topologically associating domain (TAD) organization. We employed an in situ Hi-C approach to follow the 3D organization of the fission yeast genome during the cell cycle. We demonstrate that during mitosis, large domains of 300 kb–1 Mb are formed by condensin. This mitotic domain organization does not suddenly dissolve, but gradually diminishes until the next mitosis. By contrast, small domains of 30–40 kb that are formed by cohesin are relatively stable across the cell cycle. Condensin and cohesin mediate long- and short-range contacts, respectively, by bridging their binding sites, thereby forming the large and small domains. These domains are inversely regulated during the cell cycle but assemble independently. Our study describes the chromosomal oscillation between the formation and decay phases of the large and small domains, and we predict that the condensin-mediated domains serve as chromosomal compaction units.
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