title: XCtBP is a XTcf-3 co-repressor with roles throughout Xenopus development.
abstract: XTcf-3 is an HMG box transcription factor that mediates Xenopus dorsal-ventral axis formation. As a Wnt pathway effector, XTcf-3 interacts with beta-catenin and activates the expression of the dorsal organizing gene siamois, while in the absence of beta-catenin, XTcf-3 functions as a transcriptional repressor. We show that XTcf-3 contains amino- and carboxy-terminal repressor domains and have identified a Xenopus member of the C-terminal Binding Protein family of transcriptional co-repressors (XCtBP) as the C-terminal co-repressor. We show that two XCtBP binding sites near the XTcf-3 carboxy-terminus are required for the interaction of XTcf-3 and XCtBP and for the transcriptional repression mediated by the XTcf-3 carboxy-terminal domain. By fusing the GAL4 activation domain to XCtBP we have generated an antimorphic protein, XCtBP/G4A, that activates siamois transcription through an interaction with endogenous XTcf-3. Ectopic expression of XCtBP/G4A demonstrates that XCtBP functions in the regulation of head and notochord development. Our data support a role for XCtBP as a co-repressor throughout Xenopus development and indicate that XCtBP/G4A will be a useful tool in determining how XCtBP functions in various developmental processes.
authors.affiliation: Department of Biochemistry, Howard Hughes Medical Institute, Center for Developmental Biology, University of Washington School of Medicine, Seattle, Washington 98195-7350, USA. kimelman@u.washington.edu.
authors.forename: M
authors.initials: M
authors.lastname: Brannon
authors.forename: J D
authors.initials: JD
authors.lastname: Brown
authors.forename: R
authors.initials: R
authors.lastname: Bates
authors.forename: D
authors.initials: D
authors.lastname: Kimelman
authors.forename: R T
authors.initials: RT
authors.lastname: Moon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D017124:Conserved Sequence; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D024002:HMGB Proteins; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006822:Hybrid Cells; D051821:Lymphoid Enhancer-Binding Factor 1; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D051820:TCF Transcription Factors; D013963:Thyroid Hormones; D058127:Transcription Factor 3; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014981:Xenopus / Q000196:embryology* / Q000235:genetics; D029867:Xenopus Proteins; D015003:Yeasts / Q000235:genetics; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D002352:Carrier Proteins; D024002:HMGB Proteins; D006609:High Mobility Group Proteins; D018398:Homeodomain Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D008565:Membrane Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D051820:TCF Transcription Factors; D013963:Thyroid Hormones; D058127:Transcription Factor 3; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; D029867:Xenopus Proteins; D000097810:Thyroid Hormone-Binding Proteins; C116548:Lef1 protein, Xenopus; C093133:SIA1 protein, Xenopus; C544917:Tcf3 protein, Xenopus