title: Extended HSR/CARD domain mediates AIRE binding to DNA.
abstract: Autoimmune regulator (AIRE) activates the transcription of many genes in an unusual promiscuous and stochastic manner. The mechanism by which AIRE binds to the chromatin and DNA is not fully understood, and the regulatory elements that AIRE target genes possess are not delineated. In the current study, we demonstrate that AIRE activates the expression of transiently transfected luciferase reporters that lack defined promoter regions, as well as intron and poly(A) signal sequences. Our protein-DNA interaction experiments with mutated AIRE reveal that the intact homogeneously staining region/caspase recruitment domain (HSR/CARD) and amino acids R113 and K114 are key elements involved in AIRE binding to DNA.
authors.affiliation: Molecular Pathology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, 50411, Estonia. Electronic address: julia.maslovskaja@ut.ee.
authors.forename: Julia
authors.initials: J
authors.lastname: Maslovskaja
authors.affiliation: Molecular Pathology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, 50411, Estonia.
authors.forename: Mario
authors.initials: M
authors.lastname: Saare
authors.affiliation: Molecular Pathology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, 50411, Estonia.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Liiv
authors.affiliation: Molecular Pathology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, 50411, Estonia.
authors.forename: Ana
authors.initials: A
authors.lastname: Rebane
authors.affiliation: Molecular Pathology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, 50411, Estonia.
authors.forename: Pärt
authors.initials: P
authors.lastname: Peterson
mesh_terms: D001665:Binding Sites; D053468:CARD Signaling Adaptor Proteins / Q000737:chemistry* / Q000378:metabolism*; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D011485:Protein Binding; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*; D000096927:AIRE Protein
chemical_list: D053468:CARD Signaling Adaptor Proteins; D004247:DNA; D014157:Transcription Factors; D000096927:AIRE Protein
keywords: AIRE; APECED; DNA binding; Gene activation; HSR/CARD