Aberrant transcriptional regulatory network in T cells of multiple sclerosis.
To identify the molecular network of the genes deregulated in multiple sclerosis (MS), we studied gene expression profile of purified CD3(+) T cells isolated from Hungarian monozygotic MS twins by DNA microarray analysis. By comparing three concordant and one discordant pairs, we identified 20 differentially expressed genes (DEG) between the MS patient and the genetically identical healthy subject. Molecular network of 20 DEG analyzed by KeyMolnet, a comprehensive information platform, indicated the close relationship with transcriptional regulation by the Ets transcription factor family and the nuclear factor NF-kappaB. This novel bioinformatic approach proposes the logical hypothesis that aberrant regulation of the complex transcriptional regulatory network contributes to development of pathogenic T cells in MS.
Satoh
Jun-ichi
J
Department of Bioinformatics, Meiji Pharmaceutical University, Tokyo, Japan. satoj@my-pharm.ac.jp
Illes
Zsolt
Z
Peterfalvi
Agnes
A
Tabunoki
Hiroko
H
Rozsa
Csilla
C
Yamamura
Takashi
T
D000293:Adolescent; D000465:Algorithms; D017252:CD3 Complex / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D019295:Computational Biology; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D053263:Gene Regulatory Networks / Q000235:genetics*; D006801:Humans; D006814:Hungary; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018401:Sample Size; D013601:T-Lymphocytes / Q000502:physiology*; D014427:Twins
D017252:CD3 Complex; D018076:DNA, Complementary; D050783:Proto-Oncogene Proteins c-ets