Wnt-Mediated Repression via Bipartite DNA Recognition by TCF in the Hematopoietic System

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During development and in adult tissues, cells communicate with each other through biochemical cascades known as signaling pathways. In this report, we study the Wnt signaling pathway, using the fruit fly Drosophila as a model system. This pathway is known to activate gene expression in cells receiving the Wnt signal, working through a transcription factor known as TCF. But sometimes Wnt signaling also instructs TCF to repress target gene expression. What determines whether TCF will positively or negatively regulate Wnt targets? We demonstrate that activated and repressed targets have distinct DNA sequences that dock TCF on their regulatory DNA. The type of site determines the output, i.e., activation or repression. We find that TCF adopts different conformations when bound to either DNA sequence, which most likely influences its regulatory activity. In addition, we demonstrate that Wnt-dependent repression occurs robustly in the fly larval lymph gland, the tissue responsible for generating macrophage-like cells known as hemocytes.

Vyšlo v časopise: Wnt-Mediated Repression via Bipartite DNA Recognition by TCF in the Hematopoietic System. PLoS Genet 10(8): e32767. doi:10.1371/journal.pgen.1004509
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004509

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