Transcription factor ICBP90 regulates the MIF promoter and immune susceptibility locus
作者： Jie Yao , Lin Leng , Maor Sauler , Weiling Fu , Junsong Zheng
DOI: 10.1172/JCI81937
关键词:
摘要: The immunoregulatory cytokine macrophage migration inhibitory factor (MIF) is encoded in a functionally polymorphic locus that linked to the susceptibility of autoimmune and infectious diseases. MIF promoter contains 4-nucleotide microsatellite polymorphism (-794 CATT) repeats 5 8 times locus, with greater numbers associated higher mRNA levels. Because there no information about transcriptional regulation these common alleles, we used oligonucleotide affinity chromatography liquid chromatography-mass spectrometry identify nuclear proteins interact -794 CATT5-8 site. An analysis monocyte lysates revealed transcription ICBP90 (also known as UHRF1) major protein interacting microsatellite. We found essential for from monocytes/macrophages, B T lymphocytes, synovial fibroblasts, TLR-induced regulated an ICBP90- length-dependent manner. Whole-genome shRNA-treated rheumatoid synoviocytes uncovered subset proinflammatory immune response genes overlapped those by shRNA. In addition, expression levels were correlated joint synovia patients arthritis. These findings key regulator provide functional insight into locus.
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