A new perspective on transcriptional system regulation (TSR): towards TSR profiling.

It has been hypothesized that the net expression of a gene is determined by the combined effects of various transcriptional system regulators (TSRs). However, characterizing the complexity of regulation of the transcriptome is a major challenge. Principal component analysis on 17,550 heterogeneous h...

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Autores principales: Rudolf S N Fehrmann, Hendrik J M de Jonge, Arja Ter Elst, André de Vries, Anne G P Crijns, Alida C Weidenaar, Frans Gerbens, Steven de Jong, Ate G J van der Zee, Elisabeth G E de Vries, Willem A Kamps, Robert M W Hofstra, Gerard J Te Meerman, Eveline S J M de Bont
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Publicado: Public Library of Science (PLoS) 2008
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spelling oai:doaj.org-article:951a103368b5495f8c4a0af886307e672021-11-25T06:13:18ZA new perspective on transcriptional system regulation (TSR): towards TSR profiling.1932-620310.1371/journal.pone.0001656https://doaj.org/article/951a103368b5495f8c4a0af886307e672008-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18297136/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203It has been hypothesized that the net expression of a gene is determined by the combined effects of various transcriptional system regulators (TSRs). However, characterizing the complexity of regulation of the transcriptome is a major challenge. Principal component analysis on 17,550 heterogeneous human microarray experiments revealed that 50 orthogonal factors (hereafter called TSRs) are able to capture 64% of the variability in expression in a wide range of experimental conditions and tissues. We identified gene clusters controlled in the same direction and show that gene expression can be conceptualized as a process influenced by a fairly limited set of TSRs. Furthermore, TSRs can be linked to biological functions, as we demonstrate a strong relation between TSR-related gene clusters and biological functionality as well as cellular localization, i.e. gene products of similarly regulated genes by a specific TSR are located in identical parts of a cell. Using 3,934 diverse mouse microarray experiments we found striking similarities in transcriptional system regulation between human and mouse. Our results give biological insights into regulation of the cellular transcriptome and provide a tool to characterize expression profiles with highly reliable TSRs instead of thousands of individual genes, leading to a >500-fold reduction of complexity with just 50 TSRs. This might open new avenues for those performing gene expression profiling studies.Rudolf S N FehrmannHendrik J M de JongeArja Ter ElstAndré de VriesAnne G P CrijnsAlida C WeidenaarFrans GerbensSteven de JongAte G J van der ZeeElisabeth G E de VriesWillem A KampsRobert M W HofstraGerard J Te MeermanEveline S J M de BontPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 2, p e1656 (2008)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Rudolf S N Fehrmann
Hendrik J M de Jonge
Arja Ter Elst
André de Vries
Anne G P Crijns
Alida C Weidenaar
Frans Gerbens
Steven de Jong
Ate G J van der Zee
Elisabeth G E de Vries
Willem A Kamps
Robert M W Hofstra
Gerard J Te Meerman
Eveline S J M de Bont
A new perspective on transcriptional system regulation (TSR): towards TSR profiling.
description It has been hypothesized that the net expression of a gene is determined by the combined effects of various transcriptional system regulators (TSRs). However, characterizing the complexity of regulation of the transcriptome is a major challenge. Principal component analysis on 17,550 heterogeneous human microarray experiments revealed that 50 orthogonal factors (hereafter called TSRs) are able to capture 64% of the variability in expression in a wide range of experimental conditions and tissues. We identified gene clusters controlled in the same direction and show that gene expression can be conceptualized as a process influenced by a fairly limited set of TSRs. Furthermore, TSRs can be linked to biological functions, as we demonstrate a strong relation between TSR-related gene clusters and biological functionality as well as cellular localization, i.e. gene products of similarly regulated genes by a specific TSR are located in identical parts of a cell. Using 3,934 diverse mouse microarray experiments we found striking similarities in transcriptional system regulation between human and mouse. Our results give biological insights into regulation of the cellular transcriptome and provide a tool to characterize expression profiles with highly reliable TSRs instead of thousands of individual genes, leading to a >500-fold reduction of complexity with just 50 TSRs. This might open new avenues for those performing gene expression profiling studies.
format article
author Rudolf S N Fehrmann
Hendrik J M de Jonge
Arja Ter Elst
André de Vries
Anne G P Crijns
Alida C Weidenaar
Frans Gerbens
Steven de Jong
Ate G J van der Zee
Elisabeth G E de Vries
Willem A Kamps
Robert M W Hofstra
Gerard J Te Meerman
Eveline S J M de Bont
author_facet Rudolf S N Fehrmann
Hendrik J M de Jonge
Arja Ter Elst
André de Vries
Anne G P Crijns
Alida C Weidenaar
Frans Gerbens
Steven de Jong
Ate G J van der Zee
Elisabeth G E de Vries
Willem A Kamps
Robert M W Hofstra
Gerard J Te Meerman
Eveline S J M de Bont
author_sort Rudolf S N Fehrmann
title A new perspective on transcriptional system regulation (TSR): towards TSR profiling.
title_short A new perspective on transcriptional system regulation (TSR): towards TSR profiling.
title_full A new perspective on transcriptional system regulation (TSR): towards TSR profiling.
title_fullStr A new perspective on transcriptional system regulation (TSR): towards TSR profiling.
title_full_unstemmed A new perspective on transcriptional system regulation (TSR): towards TSR profiling.
title_sort new perspective on transcriptional system regulation (tsr): towards tsr profiling.
publisher Public Library of Science (PLoS)
publishDate 2008
url https://doaj.org/article/951a103368b5495f8c4a0af886307e67
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