title: Distinct contributions of conserved modules to Runt transcription factor activity.
abstract: Runx proteins play vital roles in regulating transcription in numerous developmental pathways throughout the animal kingdom. Two Runx protein hallmarks are the DNA-binding Runt domain and a C-terminal VWRPY motif that mediates interaction with TLE/Gro corepressor proteins. A phylogenetic analysis of Runt, the founding Runx family member, identifies four distinct regions C-terminal to the Runt domain that are conserved in Drosophila and other insects. We used a series of previously described ectopic expression assays to investigate the functions of these different conserved regions in regulating gene expression during embryogenesis and in controlling axonal projections in the developing eye. The results indicate each conserved region is required for a different subset of activities and identify distinct regions that participate in the transcriptional activation and repression of the segmentation gene sloppy-paired-1 (slp1). Interestingly, the C-terminal VWRPY-containing region is not required for repression but instead plays a role in slp1 activation. Genetic experiments indicating that Groucho (Gro) does not participate in slp1 regulation further suggest that Runt's conserved C-terminus interacts with other factors to promote transcriptional activation. These results provide a foundation for further studies on the molecular interactions that contribute to the context-dependent properties of Runx proteins as developmental regulators.
authors.affiliation: Department of Biochemistry and Cell Biology and the Center for Developmental Genetics, Graduate Programs in Molecular and Cellular Biology and Biochemistry and Structural Biology, Stony Brook University, Stony Brook, NY 11794-5215, USA.
authors.forename: Pegine B
authors.initials: PB
authors.lastname: Walrad
authors.forename: Saiyu
authors.initials: S
authors.lastname: Hang
authors.forename: Genevieve S
authors.initials: GS
authors.lastname: Joseph
authors.forename: Julia
authors.initials: J
authors.lastname: Salas
authors.forename: J Peter
authors.initials: JP
authors.lastname: Gergen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D050657:Core Binding Factor alpha Subunits / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism; D007313:Insecta / Q000145:classification / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D050657:Core Binding Factor alpha Subunits; D029721:Drosophila Proteins; D056284:Histone Deacetylase 1; D012097:Repressor Proteins; D014157:Transcription Factors; C091023:gro protein, Drosophila; C074838:slp1 protein, Drosophila; C512966:HDAC1 protein, Drosophila
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