title: Multiple Arkadia/RNF111 structures coordinate its Polycomb body association and transcriptional control.
abstract: The RING domain protein Arkadia/RNF111 is a ubiquitin ligase in the transforming growth factor β (TGFβ) pathway. We previously identified Arkadia as a small ubiquitin-like modifier (SUMO)-binding protein with clustered SUMO-interacting motifs (SIMs) that together form a SUMO-binding domain (SBD). However, precisely how SUMO interaction contributes to the function of Arkadia was not resolved. Through analytical molecular and cell biology, we found that the SIMs share redundant function with Arkadia's M domain, a region distinguishing Arkadia from its paralogs ARKL1/ARKL2 and the prototypical SUMO-targeted ubiquitin ligase (STUbL) RNF4. The SIMs and M domain together promote both Arkadia's colocalization with CBX4/Pc2, a component of Polycomb bodies, and the activation of a TGFβ pathway transcription reporter. Transcriptome profiling through RNA sequencing showed that Arkadia can both promote and inhibit gene expression, indicating that Arkadia's activity in transcriptional control may depend on the epigenetic context, defined by Polycomb repressive complexes and DNA methylation.
authors.affiliation: Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California, USA hsun@salk.edu hunter@salk.edu.
authors.forename: Huaiyu
authors.initials: H
authors.lastname: Sun
authors.affiliation: Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California, USA.
authors.forename: Yijing
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California, USA hsun@salk.edu hunter@salk.edu.
authors.forename: Tony
authors.initials: T
authors.lastname: Hunter
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics; D019175:DNA Methylation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D008025:Ligases; D051379:Mice; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D063146:Polycomb-Group Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D012568:Schizosaccharomyces / Q000235:genetics; D017423:Sequence Analysis, RNA; D015398:Signal Transduction / Q000235:genetics; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D008025:Ligases; D009687:Nuclear Proteins; D063146:Polycomb-Group Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D044767:Ubiquitin-Protein Ligases; C586439:ARK2N protein, human; C114070:RNF4 protein, human; C486067:RNF111 protein, human; C570427:CBX4 protein, human