Title: High throughput genomic screen identifies multiple factors that promote cooperative Wnt signaling.
Authors: Miller, Mayumi F; Cohen, Ethan David; Baggs, Julie E; Hogenesch, John B; Morrisey, Edward E
Published In PLoS One, (2013)
Abstract: Previous studies have demonstrated that certain Wnt ligands can promote high levels of cooperative signaling in a cell type specific manner. To explore the underlying mechanism of this cooperative Wnt signaling, we performed a high-throughput screen of more than 14,000 cDNAs to identify genes that promote cooperative Wnt signaling in the context of a single Wnt ligand, Wnt2. This screen identified several homeobox factors including Msx2, Nkx5.2, and Esx1, in addition to other factors known to promote Wnt signaling including Pias4. Generation of dominant-active or dominant-negative forms of Msx2 indicate that the mechanism by which homeobox factors cooperatively promote Wnt signaling is through their ability to repress gene transcription. These data identify a broad homeobox code, which acts to increase Wnt signaling through transcriptional repression.
PubMed ID: 23383281
MeSH Terms: Cell Line; Gene Expression Profiling; Gene Expression Regulation; Genomics*/methods; High-Throughput Screening Assays; Homeodomain Proteins/genetics; Homeodomain Proteins/metabolism; Humans; Ligands; Protein Binding; Transcription Factors/genetics; Transcription Factors/metabolism; Transcription, Genetic; Wnt Proteins/metabolism*; Wnt Signaling Pathway*