Prediction of IFN-gamma regulated gene transcription.
IFN-gamma, a cytokine promoting cell-mediated immunity and antiviral effects, regulates the expression of a large set of genes involved in the immune response. Based on logistic regression, an in silico model for predicting IFN-gamma regulated transcription has been developed by scoring the transcription factor binding sites on the putative promoters of regulated versus not regulated genes derived from the microarray data of IFN-gamma treated human macrophages. The model effectively discriminates the transcription factor binding sites that confer responsiveness to IFN-gamma from those that do not. The model has 65% true positive and 22% false positive rates when evaluated on a small validation set. In order to identify potential IFN-gamma regulated genes in the whole genome, the model has been used to screen 13,668 promoter pairs of human-mouse orthologs/homologs from Ensembl, and 1,387 of them were predicted to be potentially regulated by IFN-gamma. In the pilot experiment, the regulation pattern of a subset of predicted genes that were not detected by microarray approach was evaluated by quantitative PCR. The results for the four novel genes, which are up regulated by IFN-gamma in human macrophages and identified by this approach, are described in the present communication.
Liu
Hong
H
Immunology Platform, Aventis Pharmaceuticals Inc., Route 202/206, Bridgewater, NJ 08807, USA. hong.liu@aventis.com
Ge
Nanxiang
N
Yu
Kin-Tak
KT
Krolikowski
David
D
Zilberstein
Asher
A
Hahn
Chang S
CS
D000818:Animals; D019295:Computational Biology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D014157:Transcription Factors; D007371:Interferon-gamma