Premium
Differential regulation of myc homologs by Wnt/β‐Catenin signaling in the early metazoan Hydra
Author(s) -
Hartl Markus,
Glasauer Stella,
Gufler Sabine,
Raffeiner Andrea,
Puglisi Kane,
Breuker Kathrin,
Bister Klaus,
Hobmayer Bert
Publication year - 2019
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14812
Subject(s) - lernaean hydra , biology , wnt signaling pathway , transcription factor , ectopic expression , microbiology and biotechnology , signal transduction , promoter , gene , catenin , genetics , gene expression
The c‐Myc protein is a transcription factor with oncogenic potential controlling fundamental cellular processes. Homologs of the human c‐ myc protooncogene have been identified in the early diploblastic cnidarian Hydra ( myc1 , myc2 ). The ancestral Myc1 and Myc2 proteins display the principal design and biochemical properties of their vertebrate derivatives, suggesting that important Myc functions arose very early in metazoan evolution. c‐Myc is part of a transcription factor network regulated by several upstream pathways implicated in oncogenesis and development. One of these signaling cascades is the Wnt/β‐Catenin pathway driving cell differentiation and developmental patterning, but also tumorigenic processes including aberrant transcriptional activation of c‐ myc in several human cancers. Here, we show that genetic or pharmacological stimulation of Wnt/β‐Catenin signaling in Hydra is accompanied by specific downregulation of myc1 at mRNA and protein levels. The myc1 and myc2 promoter regions contain consensus binding sites for the transcription factor Tcf, and Hydra Tcf binds to the regulatory regions of both promoters. The myc1 promoter is also specifically repressed in the presence of ectopic Hydra β‐Catenin/Tcf in avian cell culture. We propose that Hydra myc1 is a negative Wnt signaling target, in contrast to vertebrate c‐ myc , which is one of the best studied genes activated by this pathway. On the contrary, myc2 is not suppressed by ectopic β‐Catenin in Hydra and presumably represents the structural and functional c‐ myc ortholog. Our data implicate that the connection between β‐Catenin‐mediated signaling and myc1 and myc2 gene regulation is an ancestral metazoan feature. Its impact on decision making in Hydra interstitial stem cells is discussed.