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Dissecting the fission yeast regulatory network reveals phase-specific control elements of its cell cycle
BACKGROUND: Fission yeast Schizosaccharomyces pombe and budding yeast Saccharomyces cerevisiae are among the original model organisms in the study of the cell-division cycle. Unlike budding yeast, no large-scale regulatory network has been constructed for fission yeast. It has only been partially ch...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2758837/ https://www.ncbi.nlm.nih.gov/pubmed/19758441 http://dx.doi.org/10.1186/1752-0509-3-93 |
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author | Bushel, Pierre R Heard, Nicholas A Gutman, Roee Liu, Liwen Peddada, Shyamal D Pyne, Saumyadipta |
author_facet | Bushel, Pierre R Heard, Nicholas A Gutman, Roee Liu, Liwen Peddada, Shyamal D Pyne, Saumyadipta |
author_sort | Bushel, Pierre R |
collection | PubMed |
description | BACKGROUND: Fission yeast Schizosaccharomyces pombe and budding yeast Saccharomyces cerevisiae are among the original model organisms in the study of the cell-division cycle. Unlike budding yeast, no large-scale regulatory network has been constructed for fission yeast. It has only been partially characterized. As a result, important regulatory cascades in budding yeast have no known or complete counterpart in fission yeast. RESULTS: By integrating genome-wide data from multiple time course cell cycle microarray experiments we reconstructed a gene regulatory network. Based on the network, we discovered in addition to previously known regulatory hubs in M phase, a new putative regulatory hub in the form of the HMG box transcription factor SPBC19G7.04. Further, we inferred periodic activities of several less known transcription factors over the course of the cell cycle, identified over 500 putative regulatory targets and detected many new phase-specific and conserved cis-regulatory motifs. In particular, we show that SPBC19G7.04 has highly significant periodic activity that peaks in early M phase, which is coordinated with the late G2 activity of the forkhead transcription factor fkh2. Finally, using an enhanced Bayesian algorithm to co-cluster the expression data, we obtained 31 clusters of co-regulated genes 1) which constitute regulatory modules from different phases of the cell cycle, 2) whose phase order is coherent across the 10 time course experiments, and 3) which lead to identification of phase-specific control elements at both the transcriptional and post-transcriptional levels in S. pombe. In particular, the ribosome biogenesis clusters expressed in G2 phase reveal new, highly conserved RNA motifs. CONCLUSION: Using a systems-level analysis of the phase-specific nature of the S. pombe cell cycle gene regulation, we have provided new testable evidence for post-transcriptional regulation in the G2 phase of the fission yeast cell cycle. Based on this comprehensive gene regulatory network, we demonstrated how one can generate and investigate plausible hypotheses on fission yeast cell cycle regulation which can potentially be explored experimentally. |
format | Text |
id | pubmed-2758837 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-27588372009-10-08 Dissecting the fission yeast regulatory network reveals phase-specific control elements of its cell cycle Bushel, Pierre R Heard, Nicholas A Gutman, Roee Liu, Liwen Peddada, Shyamal D Pyne, Saumyadipta BMC Syst Biol Research Article BACKGROUND: Fission yeast Schizosaccharomyces pombe and budding yeast Saccharomyces cerevisiae are among the original model organisms in the study of the cell-division cycle. Unlike budding yeast, no large-scale regulatory network has been constructed for fission yeast. It has only been partially characterized. As a result, important regulatory cascades in budding yeast have no known or complete counterpart in fission yeast. RESULTS: By integrating genome-wide data from multiple time course cell cycle microarray experiments we reconstructed a gene regulatory network. Based on the network, we discovered in addition to previously known regulatory hubs in M phase, a new putative regulatory hub in the form of the HMG box transcription factor SPBC19G7.04. Further, we inferred periodic activities of several less known transcription factors over the course of the cell cycle, identified over 500 putative regulatory targets and detected many new phase-specific and conserved cis-regulatory motifs. In particular, we show that SPBC19G7.04 has highly significant periodic activity that peaks in early M phase, which is coordinated with the late G2 activity of the forkhead transcription factor fkh2. Finally, using an enhanced Bayesian algorithm to co-cluster the expression data, we obtained 31 clusters of co-regulated genes 1) which constitute regulatory modules from different phases of the cell cycle, 2) whose phase order is coherent across the 10 time course experiments, and 3) which lead to identification of phase-specific control elements at both the transcriptional and post-transcriptional levels in S. pombe. In particular, the ribosome biogenesis clusters expressed in G2 phase reveal new, highly conserved RNA motifs. CONCLUSION: Using a systems-level analysis of the phase-specific nature of the S. pombe cell cycle gene regulation, we have provided new testable evidence for post-transcriptional regulation in the G2 phase of the fission yeast cell cycle. Based on this comprehensive gene regulatory network, we demonstrated how one can generate and investigate plausible hypotheses on fission yeast cell cycle regulation which can potentially be explored experimentally. BioMed Central 2009-09-16 /pmc/articles/PMC2758837/ /pubmed/19758441 http://dx.doi.org/10.1186/1752-0509-3-93 Text en Copyright © 2009 Bushel et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Bushel, Pierre R Heard, Nicholas A Gutman, Roee Liu, Liwen Peddada, Shyamal D Pyne, Saumyadipta Dissecting the fission yeast regulatory network reveals phase-specific control elements of its cell cycle |
title | Dissecting the fission yeast regulatory network reveals phase-specific control elements of its cell cycle |
title_full | Dissecting the fission yeast regulatory network reveals phase-specific control elements of its cell cycle |
title_fullStr | Dissecting the fission yeast regulatory network reveals phase-specific control elements of its cell cycle |
title_full_unstemmed | Dissecting the fission yeast regulatory network reveals phase-specific control elements of its cell cycle |
title_short | Dissecting the fission yeast regulatory network reveals phase-specific control elements of its cell cycle |
title_sort | dissecting the fission yeast regulatory network reveals phase-specific control elements of its cell cycle |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2758837/ https://www.ncbi.nlm.nih.gov/pubmed/19758441 http://dx.doi.org/10.1186/1752-0509-3-93 |
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