RDF/XMLNTriplesTurtleShow queryShare
SubjectPredicateObject
http://purl.uniprot.org/citations/19293276http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19293276http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19293276http://www.w3.org/2000/01/rdf-schema#comment"Plant homeodomain (PHD) fingers are often present in chromatin-binding proteins and have been shown to bind histone H3 N-terminal tails. Mutations in the autoimmune regulator (AIRE) protein, which harbours two PHD fingers, cause a rare monogenic disease, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). AIRE activates the expression of tissue-specific antigens by directly binding through its first PHD finger (AIRE-PHD1) to histone H3 tails non-methylated at K4 (H3K4me0). Here, we present the solution structure of AIRE-PHD1 in complex with H3K4me0 peptide and show that AIRE-PHD1 is a highly specialized non-modified histone H3 tail reader, as post-translational modifications of the first 10 histone H3 residues reduce binding affinity. In particular, H3R2 dimethylation abrogates AIRE-PHD1 binding in vitro and reduces the in vivo activation of AIRE target genes in HEK293 cells. The observed antagonism by R2 methylation on AIRE-PHD1 binding is unique among the H3K4me0 histone readers and represents the first case of epigenetic negative cross-talk between non-methylated H3K4 and methylated H3R2. Collectively, our results point to a very specific histone code responsible for non-modified H3 tail recognition by AIRE-PHD1 and describe at atomic level one crucial step in the molecular mechanism responsible for antigen expression in the thymus."xsd:string
http://purl.uniprot.org/citations/19293276http://purl.org/dc/terms/identifier"doi:10.1093/nar/gkp166"xsd:string
http://purl.uniprot.org/citations/19293276http://purl.org/dc/terms/identifier"doi:10.1093/nar/gkp166"xsd:string
http://purl.uniprot.org/citations/19293276http://purl.uniprot.org/core/author"Gaetani M."xsd:string
http://purl.uniprot.org/citations/19293276http://purl.uniprot.org/core/author"Gaetani M."xsd:string
http://purl.uniprot.org/citations/19293276http://purl.uniprot.org/core/author"Chignola F."xsd:string
http://purl.uniprot.org/citations/19293276http://purl.uniprot.org/core/author"Chignola F."xsd:string
http://purl.uniprot.org/citations/19293276http://purl.uniprot.org/core/author"Mannella V."xsd:string
http://purl.uniprot.org/citations/19293276http://purl.uniprot.org/core/author"Mannella V."xsd:string
http://purl.uniprot.org/citations/19293276http://purl.uniprot.org/core/author"Mollica L."xsd:string
http://purl.uniprot.org/citations/19293276http://purl.uniprot.org/core/author"Mollica L."xsd:string
http://purl.uniprot.org/citations/19293276http://purl.uniprot.org/core/author"Musco G."xsd:string
http://purl.uniprot.org/citations/19293276http://purl.uniprot.org/core/author"Musco G."xsd:string
http://purl.uniprot.org/citations/19293276http://purl.uniprot.org/core/author"Org T."xsd:string
http://purl.uniprot.org/citations/19293276http://purl.uniprot.org/core/author"Org T."xsd:string
http://purl.uniprot.org/citations/19293276http://purl.uniprot.org/core/author"Peterson P."xsd:string
http://purl.uniprot.org/citations/19293276http://purl.uniprot.org/core/author"Peterson P."xsd:string
http://purl.uniprot.org/citations/19293276http://purl.uniprot.org/core/author"Rebane A."xsd:string
http://purl.uniprot.org/citations/19293276http://purl.uniprot.org/core/author"Rebane A."xsd:string
http://purl.uniprot.org/citations/19293276http://purl.uniprot.org/core/author"Spitaleri A."xsd:string
http://purl.uniprot.org/citations/19293276http://purl.uniprot.org/core/author"Spitaleri A."xsd:string
http://purl.uniprot.org/citations/19293276http://purl.uniprot.org/core/author"Zucchelli C."xsd:string
http://purl.uniprot.org/citations/19293276http://purl.uniprot.org/core/author"Zucchelli C."xsd:string