Genome-wide profiling of target genes for the systemic lupus erythematosus-associated transcription factors IRF5 and STAT4
2013 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 72, no 1, 96-103 p.Article in journal (Refereed) Published
The transcription factors interferon regulatory factor 5 (IRF5) and signal transducer and activator of transcription 4 (STAT4) are encoded by two of the strongest susceptibility genes for systemic lupus erythematosus (SLE).
To investigate the target genes and functional roles of IRF5 and STAT4 in human peripheral blood mononuclear cells (PBMCs).
Chromatin immunoprecipitation-sequencing (ChIP-seq) was performed in PBMCs stimulated to activate IRF5 and STAT4. The expression of the target genes of IRF5 and STAT4 was investigated in a publicly available dataset generated from PBMCs from patients with SLE and healthy controls. The genomic regions bound by the transcription complexes mediated by IRF5 and STAT4 were examined for transcription factor binding motifs and SLE-associated sequence variants.
More than 7000 target genes for IRF5 and STAT4 were identified in stimulated PBMCs. These genes were enriched to functional pathways in the type I interferon system, and have key roles in the inflammatory response. The expression patterns of the target genes were characteristic for patients with SLE. The transcription factors high mobility group-I/Y, specificity protein 1, and paired box 4 may function cooperatively with IRF5 and STAT4 in transcriptional regulation. Eight of the target regions for IRF5 and STAT4 contain SLE-associated sequence variants.
By participating in transcription complex with other co-factors, IRF5 and STAT4 harbour the potential of regulating a large number of target genes, which may contribute to their strong association with SLE.
Place, publisher, year, edition, pages
2013. Vol. 72, no 1, 96-103 p.
interferon regulatory factor 5, signal transducer and activator of transcription 4, systemic lupus erythematosus, ChIP-seq
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-179118DOI: 10.1136/annrheumdis-2012-201364ISI: 000312407800016PubMedID: 22730365OAI: oai:DiVA.org:uu-179118DiVA: diva2:543452