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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: Fehrmann, Rudolf S. N., de Jonge, Hendrik J. M., ter Elst, Arja, de Vries, André, Crijns, Anne G. P., Weidenaar, Alida C., Gerbens, Frans, de Jong, Steven, van der Zee, Ate G. J., de Vries, Elisabeth G. E., Kamps, Willem A., Hofstra, Robert M. W., te Meerman, Gerard J., de Bont, Eveline S. J. M.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2250855/
https://www.ncbi.nlm.nih.gov/pubmed/18297136
http://dx.doi.org/10.1371/journal.pone.0001656
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author Fehrmann, Rudolf S. N.
de Jonge, Hendrik J. M.
ter Elst, Arja
de Vries, André
Crijns, Anne G. P.
Weidenaar, Alida C.
Gerbens, Frans
de Jong, Steven
van der Zee, Ate G. J.
de Vries, Elisabeth G. E.
Kamps, Willem A.
Hofstra, Robert M. W.
te Meerman, Gerard J.
de Bont, Eveline S. J. M.
author_facet Fehrmann, Rudolf S. N.
de Jonge, Hendrik J. M.
ter Elst, Arja
de Vries, André
Crijns, Anne G. P.
Weidenaar, Alida C.
Gerbens, Frans
de Jong, Steven
van der Zee, Ate G. J.
de Vries, Elisabeth G. E.
Kamps, Willem A.
Hofstra, Robert M. W.
te Meerman, Gerard J.
de Bont, Eveline S. J. M.
author_sort Fehrmann, Rudolf S. N.
collection PubMed
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.
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spelling pubmed-22508552008-02-23 A New Perspective on Transcriptional System Regulation (TSR): Towards TSR Profiling Fehrmann, Rudolf S. N. de Jonge, Hendrik J. M. ter Elst, Arja de Vries, André Crijns, Anne G. P. Weidenaar, Alida C. Gerbens, Frans de Jong, Steven van der Zee, Ate G. J. de Vries, Elisabeth G. E. Kamps, Willem A. Hofstra, Robert M. W. te Meerman, Gerard J. de Bont, Eveline S. J. M. PLoS One Research Article 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. Public Library of Science 2008-02-20 /pmc/articles/PMC2250855/ /pubmed/18297136 http://dx.doi.org/10.1371/journal.pone.0001656 Text en Fehrmann et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Fehrmann, Rudolf S. N.
de Jonge, Hendrik J. M.
ter Elst, Arja
de Vries, André
Crijns, Anne G. P.
Weidenaar, Alida C.
Gerbens, Frans
de Jong, Steven
van der Zee, Ate G. J.
de Vries, Elisabeth G. E.
Kamps, Willem A.
Hofstra, Robert M. W.
te Meerman, Gerard J.
de Bont, Eveline S. J. M.
A New Perspective on Transcriptional System Regulation (TSR): Towards TSR Profiling
title 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_short A New Perspective on Transcriptional System Regulation (TSR): Towards TSR Profiling
title_sort new perspective on transcriptional system regulation (tsr): towards tsr profiling
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2250855/
https://www.ncbi.nlm.nih.gov/pubmed/18297136
http://dx.doi.org/10.1371/journal.pone.0001656
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