Ets transcription factors regulate AIRE gene promoter.
Autoimmune regulator (AIRE) directs the expression of self-antigens in thymus. Defects in AIRE gene cause an organ-specific autoimmune disease called autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED). AIRE protein is mainly expressed in thymic medullary epithelial cells, thus implying a strict control over its expression pattern. To date, only limited information is available on mechanisms responsible for the regulation of AIRE gene. Here, we show that Ets transcription factor family members Ets-1, Ets-2, and ESE-1 have positive effect on AIRE transcription. Site-directed mutagenesis and transfection studies revealed that two of the three Ets binding sites in AIRE promoter are functional and this finding has been confirmed by the electrophoretic mobility shift assay. The AIRE promoter activity could be stimulated by phorbol myristate acetate (PMA) and this activation was further enhanced by Ets transcription factors. Our results demonstrate for the first time that AIRE gene is a downstream target for the Ets family of transcription factors.
Murumägi
Astrid
A
Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland. ltasmu@uta.fi
Silvennoinen
Olli
O
Peterson
Pärt
P
D001483:Base Sequence; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000502:physiology; D024202:Electrophoretic Mobility Shift Assay; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000187:drug effects; D050784:Proto-Oncogene Protein c-ets-1; D050787:Proto-Oncogene Protein c-ets-2 / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology; D050783:Proto-Oncogene Proteins c-ets / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D000096927:AIRE Protein
D004268:DNA-Binding Proteins; D050784:Proto-Oncogene Protein c-ets-1; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D013755:Tetradecanoylphorbol Acetate; D014157:Transcription Factors; D000096927:AIRE Protein; C105529:ELF3 protein, human; C494041:ETS1 protein, human