title: Activation of wingless targets requires bipartite recognition of DNA by TCF.
abstract: Specific recognition of DNA by transcription factors is essential for precise gene regulation. In Wingless (Wg) signaling in Drosophila, target gene regulation is controlled by T cell factor (TCF), which binds to specific DNA sequences through a high mobility group (HMG) domain. However, there is considerable variability in TCF binding sites, raising the possibility that they are not sufficient for target location. Some isoforms of human TCF contain a domain, termed the C-clamp, that mediates binding to an extended sequence in vitro. However, the significance of this extended sequence for the function of Wnt response elements (WREs) is unclear. In this report, we identify a cis-regulatory element that, to our knowledge, was previously unpublished. The element, named the TCF Helper site (Helper site), is essential for the activation of several WREs. This motif greatly augments the ability of TCF binding sites to respond to Wg signaling. Drosophila TCF contains a C-clamp that enhances in vitro binding to TCF-Helper site pairs and is required for transcriptional activation of WREs containing Helper sites. A genome-wide search for clusters of TCF and Helper sites identified two new WREs. Our data suggest that DNA recognition by fly TCF occurs through a bipartite mechanism, involving both the HMG domain and the C-clamp, which enables TCF to locate and activate WREs in the nucleus.
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109-1048, USA.
authors.forename: Mikyung V
authors.initials: MV
authors.lastname: Chang
authors.forename: Jinhee L
authors.initials: JL
authors.lastname: Chang
authors.forename: Anu
authors.initials: A
authors.lastname: Gangopadhyay
authors.forename: Andrew
authors.initials: A
authors.lastname: Shearer
authors.forename: Ken M
authors.initials: KM
authors.lastname: Cadigan
mesh_terms: D000818:Animals; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation; D006609:High Mobility Group Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics*; D015398:Signal Transduction; D051820:TCF Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D015533:Transcriptional Activation; D051153:Wnt Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D006609:High Mobility Group Proteins; D012097:Repressor Proteins; D051820:TCF Transcription Factors; D051153:Wnt Proteins; C115159:pan protein, Drosophila; D004247:DNA