title: The autoimmune regulator PHD finger binds to non-methylated histone H3K4 to activate gene expression.
abstract: Mutations in the gene autoimmune regulator (AIRE) cause autoimmune polyendocrinopathy candidiasis ectodermal dystrophy. AIRE is expressed in thymic medullary epithelial cells, where it promotes the expression of tissue-restricted antigens. By the combined use of biochemical and biophysical methods, we show that AIRE selectively interacts with histone H3 through its first plant homeodomain (PHD) finger (AIRE-PHD1) and preferentially binds to non-methylated H3K4 (H3K4me0). Accordingly, in vivo AIRE binds to and activates promoters containing low levels of H3K4me3 in human embryonic kidney 293 cells. We conclude that AIRE-PHD1 is an important member of a newly identified class of PHD fingers that specifically recognize H3K4me0, thus providing a new link between the status of histone modifications and the regulation of tissue-restricted antigen expression in thymus.
authors.affiliation: Molecular Pathology, University of Tartu, Tartu 50411, Estonia.
authors.forename: Tõnis
authors.initials: T
authors.lastname: Org
authors.forename: Francesca
authors.initials: F
authors.lastname: Chignola
authors.forename: Csaba
authors.initials: C
authors.lastname: Hetényi
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Gaetani
authors.forename: Ana
authors.initials: A
authors.lastname: Rebane
authors.forename: Ingrid
authors.initials: I
authors.lastname: Liiv
authors.forename: Uko
authors.initials: U
authors.lastname: Maran
authors.forename: Luca
authors.initials: L
authors.lastname: Mollica
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Bottomley
authors.forename: Giovanna
authors.initials: G
authors.lastname: Musco
authors.forename: Pärt
authors.initials: P
authors.lastname: Peterson
mesh_terms: D002151:Calorimetry; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D005786:Gene Expression Regulation / Q000235:genetics*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D016884:Polyendocrinopathies, Autoimmune / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000096927:AIRE Protein
chemical_list: D006657:Histones; D014157:Transcription Factors; D000096927:AIRE Protein