A genome-wide analysis of carbon catabolite repression in Schizosaccharomyces pombe
Abstract Background Optimal glucose metabolism is central to the growth and development of cells. In microbial eukaryotes, carbon catabolite repression (CCR) mediates the preferential utilization of glucose, primarily by repressing alternate carbon source utilization. In fission yeast, CCR is mediat...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-03-01
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| Series: | BMC Genomics |
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| Online Access: | http://link.springer.com/article/10.1186/s12864-019-5602-8 |
| _version_ | 1828169645321879552 |
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| author | Dane Vassiliadis Koon Ho Wong Alex Andrianopoulos Brendon J. Monahan |
| author_facet | Dane Vassiliadis Koon Ho Wong Alex Andrianopoulos Brendon J. Monahan |
| author_sort | Dane Vassiliadis |
| collection | DOAJ |
| description | Abstract Background Optimal glucose metabolism is central to the growth and development of cells. In microbial eukaryotes, carbon catabolite repression (CCR) mediates the preferential utilization of glucose, primarily by repressing alternate carbon source utilization. In fission yeast, CCR is mediated by transcriptional repressors Scr1 and the Tup/Ssn6 complex, with the Rst2 transcription factor important for activation of gluconeogenesis and sexual differentiation genes upon derepression. Through genetic and genome-wide methods, this study aimed to comprehensively characterize CCR in fission yeast by identifying the genes and biological processes that are regulated by Scr1, Tup/Ssn6 and Rst2, the core CCR machinery. Results The transcriptional response of fission yeast to glucose-sufficient or glucose-deficient growth conditions in wild type and CCR mutant cells was determined by RNA-seq and ChIP-seq. Scr1 was found to regulate genes involved in carbon metabolism, hexose uptake, gluconeogenesis and the TCA cycle. Surprisingly, a role for Scr1 in the suppression of sexual differentiation was also identified, as homothallic scr1 deletion mutants showed ectopic meiosis in carbon and nitrogen rich conditions. ChIP-seq characterised the targets of Tup/Ssn6 and Rst2 identifying regulatory roles within and independent of CCR. Finally, a subset of genes bound by all three factors was identified, implying that regulation of certain loci may be modulated in a competitive fashion between the Scr1, Tup/Ssn6 repressors and the Rst2 activator. Conclusions By identifying the genes directly and indirectly regulated by Scr1, Tup/Ssn6 and Rst2, this study comprehensively defined the gene regulatory networks of CCR in fission yeast and revealed the transcriptional complexities governing this system. |
| first_indexed | 2024-04-12T02:54:48Z |
| format | Article |
| id | doaj.art-0ebb4ab81a144700a87762fa46ae9bde |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-04-12T02:54:48Z |
| publishDate | 2019-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-0ebb4ab81a144700a87762fa46ae9bde2022-12-22T03:50:51ZengBMCBMC Genomics1471-21642019-03-0120111910.1186/s12864-019-5602-8A genome-wide analysis of carbon catabolite repression in Schizosaccharomyces pombeDane Vassiliadis0Koon Ho Wong1Alex Andrianopoulos2Brendon J. Monahan3Genetics, Genomics & Systems Biology, School of Biosciences, The University of MelbourneFaculty of Health Sciences, University of MacauGenetics, Genomics & Systems Biology, School of Biosciences, The University of MelbourneGenetics, Genomics & Systems Biology, School of Biosciences, The University of MelbourneAbstract Background Optimal glucose metabolism is central to the growth and development of cells. In microbial eukaryotes, carbon catabolite repression (CCR) mediates the preferential utilization of glucose, primarily by repressing alternate carbon source utilization. In fission yeast, CCR is mediated by transcriptional repressors Scr1 and the Tup/Ssn6 complex, with the Rst2 transcription factor important for activation of gluconeogenesis and sexual differentiation genes upon derepression. Through genetic and genome-wide methods, this study aimed to comprehensively characterize CCR in fission yeast by identifying the genes and biological processes that are regulated by Scr1, Tup/Ssn6 and Rst2, the core CCR machinery. Results The transcriptional response of fission yeast to glucose-sufficient or glucose-deficient growth conditions in wild type and CCR mutant cells was determined by RNA-seq and ChIP-seq. Scr1 was found to regulate genes involved in carbon metabolism, hexose uptake, gluconeogenesis and the TCA cycle. Surprisingly, a role for Scr1 in the suppression of sexual differentiation was also identified, as homothallic scr1 deletion mutants showed ectopic meiosis in carbon and nitrogen rich conditions. ChIP-seq characterised the targets of Tup/Ssn6 and Rst2 identifying regulatory roles within and independent of CCR. Finally, a subset of genes bound by all three factors was identified, implying that regulation of certain loci may be modulated in a competitive fashion between the Scr1, Tup/Ssn6 repressors and the Rst2 activator. Conclusions By identifying the genes directly and indirectly regulated by Scr1, Tup/Ssn6 and Rst2, this study comprehensively defined the gene regulatory networks of CCR in fission yeast and revealed the transcriptional complexities governing this system.http://link.springer.com/article/10.1186/s12864-019-5602-8Schizosaccharomyces pombeTranscriptional regulationCarbon metabolismCarbon catabolite repressionScr1Tup11 |
| spellingShingle | Dane Vassiliadis Koon Ho Wong Alex Andrianopoulos Brendon J. Monahan A genome-wide analysis of carbon catabolite repression in Schizosaccharomyces pombe BMC Genomics Schizosaccharomyces pombe Transcriptional regulation Carbon metabolism Carbon catabolite repression Scr1 Tup11 |
| title | A genome-wide analysis of carbon catabolite repression in Schizosaccharomyces pombe |
| title_full | A genome-wide analysis of carbon catabolite repression in Schizosaccharomyces pombe |
| title_fullStr | A genome-wide analysis of carbon catabolite repression in Schizosaccharomyces pombe |
| title_full_unstemmed | A genome-wide analysis of carbon catabolite repression in Schizosaccharomyces pombe |
| title_short | A genome-wide analysis of carbon catabolite repression in Schizosaccharomyces pombe |
| title_sort | genome wide analysis of carbon catabolite repression in schizosaccharomyces pombe |
| topic | Schizosaccharomyces pombe Transcriptional regulation Carbon metabolism Carbon catabolite repression Scr1 Tup11 |
| url | http://link.springer.com/article/10.1186/s12864-019-5602-8 |
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