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http://purl.uniprot.org/citations/22837395http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22837395http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22837395http://www.w3.org/2000/01/rdf-schema#comment"Multiple covalent modifications on a histone tail are often recognized by linked histone reader modules. UHRF1 [ubiquitin-like, containing plant homeodomain (PHD) and really interesting new gene (RING) finger domains 1], an essential factor for maintenance of DNA methylation, contains linked two-histone reader modules, a tandem Tudor domain and a PHD finger, tethered by a 17-aa linker, and has been implicated to link histone modifications and DNA methylation. Here, we present the crystal structure of the linked histone reader modules of UHRF1 in complex with the amino-terminal tail of histone H3. Our structural and biochemical data provide the basis for combinatorial readout of unmodified Arg-2 (H3-R2) and methylated Lys-9 (H3-K9) by the tandem tudor domain and the PHD finger. The structure reveals that the intermodule linker plays an essential role in the formation of a histone H3-binding hole between the reader modules by making extended contacts with the tandem tudor domain. The histone H3 tail fits into the hole by adopting a compact fold harboring a central helix, which allows both of the reader modules to simultaneously recognize the modification states at H3-R2 and H3-K9. Our data also suggest that phosphorylation of a linker residue can modulate the relative position of the reader modules, thereby altering the histone H3-binding mode. This finding implies that the linker region plays a role as a functional switch of UHRF1 involved in multiple regulatory pathways such as maintenance of DNA methylation and transcriptional repression."xsd:string
http://purl.uniprot.org/citations/22837395http://purl.org/dc/terms/identifier"doi:10.1073/pnas.1203701109"xsd:string
http://purl.uniprot.org/citations/22837395http://purl.org/dc/terms/identifier"doi:10.1073/pnas.1203701109"xsd:string
http://purl.uniprot.org/citations/22837395http://purl.uniprot.org/core/author"Oda T."xsd:string
http://purl.uniprot.org/citations/22837395http://purl.uniprot.org/core/author"Oda T."xsd:string
http://purl.uniprot.org/citations/22837395http://purl.uniprot.org/core/author"Arita K."xsd:string
http://purl.uniprot.org/citations/22837395http://purl.uniprot.org/core/author"Arita K."xsd:string
http://purl.uniprot.org/citations/22837395http://purl.uniprot.org/core/author"Sato M."xsd:string
http://purl.uniprot.org/citations/22837395http://purl.uniprot.org/core/author"Sato M."xsd:string
http://purl.uniprot.org/citations/22837395http://purl.uniprot.org/core/author"Shirakawa M."xsd:string
http://purl.uniprot.org/citations/22837395http://purl.uniprot.org/core/author"Shirakawa M."xsd:string
http://purl.uniprot.org/citations/22837395http://purl.uniprot.org/core/author"Tochio H."xsd:string
http://purl.uniprot.org/citations/22837395http://purl.uniprot.org/core/author"Tochio H."xsd:string
http://purl.uniprot.org/citations/22837395http://purl.uniprot.org/core/author"Ariyoshi M."xsd:string
http://purl.uniprot.org/citations/22837395http://purl.uniprot.org/core/author"Ariyoshi M."xsd:string
http://purl.uniprot.org/citations/22837395http://purl.uniprot.org/core/author"Unoki M."xsd:string
http://purl.uniprot.org/citations/22837395http://purl.uniprot.org/core/author"Unoki M."xsd:string
http://purl.uniprot.org/citations/22837395http://purl.uniprot.org/core/author"Hamamoto R."xsd:string
http://purl.uniprot.org/citations/22837395http://purl.uniprot.org/core/author"Hamamoto R."xsd:string
http://purl.uniprot.org/citations/22837395http://purl.uniprot.org/core/author"Sugita K."xsd:string
http://purl.uniprot.org/citations/22837395http://purl.uniprot.org/core/author"Sugita K."xsd:string
http://purl.uniprot.org/citations/22837395http://purl.uniprot.org/core/author"Isogai S."xsd:string
http://purl.uniprot.org/citations/22837395http://purl.uniprot.org/core/author"Isogai S."xsd:string