Journal article
A transcription factor map as revealed by a Genome-wide gene expression analysis of Whole-Blood mRNA transcriptome in multiple sclerosis
PloS one, Vol.5(12), e14176
2010
Abstract
Background
Several lines of evidence suggest that transcription factors are involved in the pathogenesis of Multiple Sclerosis (MS) but complete mapping of the whole network has been elusive. One of the reasons is that there are several clinical subtypes of MS and transcription factors that may be involved in one subtype may not be in others. We investigate the possibility that this network could be mapped using microarray technologies and contemporary bioinformatics methods on a dataset derived from whole blood in 99 untreated MS patients (36 Relapse Remitting MS, 43 Primary Progressive MS, and 20 Secondary Progressive MS) and 45 age-matched healthy controls.
Methodology/Principal Findings
We have used two different analytical methodologies: a non-standard differential expression analysis and a differential co-expression analysis, which have converged on a significant number of regulatory motifs that are statistically overrepresented in genes that are either differentially expressed (or differentially co-expressed) in cases and controls (e.g., V$KROX_Q6, p-value <3.31E-6; V$CREBP1_Q2, p-value <9.93E-6, V$YY1_02, p-value <1.65E-5).
Conclusions/Significance
Our analysis uncovered a network of transcription factors that potentially dysregulate several genes in MS or one or more of its disease subtypes. The most significant transcription factor motifs were for the Early Growth Response EGR/KROX family, ATF2, YY1 (Yin and Yang 1), E2F-1/DP-1 and E2F-4/DP-2 heterodimers, SOX5, and CREB and ATF families. These transcription factors are involved in early T-lymphocyte specification and commitment as well as in oligodendrocyte dedifferentiation and development, both pathways that have significant biological plausibility in MS causation.
Details
- Title
- A transcription factor map as revealed by a Genome-wide gene expression analysis of Whole-Blood mRNA transcriptome in multiple sclerosis
- Authors/Creators
- C. Riveros (Author/Creator) - Hunter Medical Research InstituteD. Mellor (Author/Creator) - Hunter Medical Research InstituteK.S. Gandhi (Author/Creator) - The University of SydneyF.C. McKay (Author/Creator) - The University of SydneyM.B. Cox (Author/Creator) - Hunter Medical Research InstituteR. Berretta (Author/Creator) - Hunter Medical Research InstituteS.Y. Vaezpour (Author/Creator) - Hunter Medical Research InstituteM. Inostroza-Ponta (Author/Creator) - Hunter Medical Research InstituteS.A. Broadley (Author/Creator) - Griffith UniversityR.N. Heard (Author/Creator) - The University of SydneyS. Vucic (Author/Creator) - The University of SydneyG.J. Stewart (Author/Creator) - The University of SydneyD.W. Williams (Author/Creator) - John Hunter HospitalR.J. Scott (Author/Creator) - Hunter Medical Research InstituteJ. Lechner-Scott (Author/Creator) - Hunter Medical Research InstituteD.R. Booth (Author/Creator) - The University of SydneyP. Moscato (Author/Creator) - Australian Research CouncilA.G. Kermode (Author/Creator)
- Publication Details
- PloS one, Vol.5(12), e14176
- Publisher
- Public Library of Science
- Identifiers
- 991005542101107891
- Copyright
- © 2010 Riveros et al.
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
- Note
- Appears as a member of the ANZgene Multiple Sclerosis Genetics Consortium
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.203 Neuromuscular Disorders
- 1.203.147 Multiple Sclerosis
- Web Of Science research areas
- Immunology
- ESI research areas
- Neuroscience & Behavior