Calculating the statistical significance of physical clusters of co-regulated genes in the genome: The role of chromatin in domain-wide gene regulation

dc.contributor.authorChang, Cheng‐Fu
dc.contributor.authorWai, Ka‐Man
dc.contributor.authorPatterton, Hugh G
dc.date.accessioned2017-11-22T14:43:48Z
dc.date.available2017-11-22T14:43:48Z
dc.date.issued2004
dc.date.updated2017-11-22T13:20:34Z
dc.description.abstractPhysical clusters of co‐regulated, but apparently functionally unrelated, genes are present in many genomes. Despite the important implication that the genomic environment contributes appreciably to the regulation of gene expression, no simple statistical method has been described to identify physical clusters of co‐regulated genes. Here we report the development of a model that allows the direct calculation of the significance of such clusters. We have implemented the derived statistical relation in a software program, Pyxis, and have analyzed a selection of Saccharomyces cerevisiae gene expression microarray data sets. We have identified many gene clusters where constituent genes exhibited a regulatory dependence on proteins previously implicated in chromatin structure. Specifically, we found that Tup1p‐dependent gene domains were enriched close to telomeres, which suggested a new role for Tup1p in telomere silencing. In addition, we identified Sir2p‐, Sir3p‐ and Sir4p‐dependent clusters, which suggested the presence of Sir‐mediated heterochromatin in previously unidentified regions of the yeast genome. We also showed the presence of Sir4p‐dependent gene clusters bordering the HMRaheterothallic locus, which suggested leaky termination of the heterochromatin by the boundary elements. These results demonstrate the utility of Pyxis in identifying possible higher order genomic features that may contribute to gene regulation in extended domains.
dc.identifierhttp://dx.doi.org/10.1093/nar/gkh507
dc.identifier.apacitation, , & Patterton, H. G. (2004). Calculating the statistical significance of physical clusters of co-regulated genes in the genome: The role of chromatin in domain-wide gene regulation. <i>Nucleic Acids Research</i>, http://hdl.handle.net/11427/26414en_ZA
dc.identifier.chicagocitation, , and Hugh G Patterton "Calculating the statistical significance of physical clusters of co-regulated genes in the genome: The role of chromatin in domain-wide gene regulation." <i>Nucleic Acids Research</i> (2004) http://hdl.handle.net/11427/26414en_ZA
dc.identifier.citationChang, C. F., Wai, K. M., & Patterton, H. G. (2004). Calculating the statistical significance of physical clusters of co‐regulated genes in the genome: the role of chromatin in domain‐wide gene regulation. Nucleic acids research, 32(5), 1798-1807.
dc.identifier.ris TY - Journal Article AU - Chang, Cheng‐Fu AU - Wai, Ka‐Man AU - Patterton, Hugh G AB - Physical clusters of co‐regulated, but apparently functionally unrelated, genes are present in many genomes. Despite the important implication that the genomic environment contributes appreciably to the regulation of gene expression, no simple statistical method has been described to identify physical clusters of co‐regulated genes. Here we report the development of a model that allows the direct calculation of the significance of such clusters. We have implemented the derived statistical relation in a software program, Pyxis, and have analyzed a selection of Saccharomyces cerevisiae gene expression microarray data sets. We have identified many gene clusters where constituent genes exhibited a regulatory dependence on proteins previously implicated in chromatin structure. Specifically, we found that Tup1p‐dependent gene domains were enriched close to telomeres, which suggested a new role for Tup1p in telomere silencing. In addition, we identified Sir2p‐, Sir3p‐ and Sir4p‐dependent clusters, which suggested the presence of Sir‐mediated heterochromatin in previously unidentified regions of the yeast genome. We also showed the presence of Sir4p‐dependent gene clusters bordering the HMRaheterothallic locus, which suggested leaky termination of the heterochromatin by the boundary elements. These results demonstrate the utility of Pyxis in identifying possible higher order genomic features that may contribute to gene regulation in extended domains. DA - 2004 DB - OpenUCT DP - University of Cape Town J1 - Nucleic Acids Research LK - https://open.uct.ac.za PB - University of Cape Town PY - 2004 T1 - Calculating the statistical significance of physical clusters of co-regulated genes in the genome: The role of chromatin in domain-wide gene regulation TI - Calculating the statistical significance of physical clusters of co-regulated genes in the genome: The role of chromatin in domain-wide gene regulation UR - http://hdl.handle.net/11427/26414 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/26414
dc.identifier.vancouvercitation, , Patterton HG. Calculating the statistical significance of physical clusters of co-regulated genes in the genome: The role of chromatin in domain-wide gene regulation. Nucleic Acids Research. 2004; http://hdl.handle.net/11427/26414.en_ZA
dc.language.isoeng
dc.publisher.departmentDepartment of Molecular and Cell Biologyen_ZA
dc.publisher.facultyFaculty of Scienceen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.sourceNucleic Acids Research
dc.source.urihttps://academic.oup.com/nar
dc.subject.otherComputational Methods
dc.titleCalculating the statistical significance of physical clusters of co-regulated genes in the genome: The role of chromatin in domain-wide gene regulation
dc.typeJournal Article
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