Abstract
Wnt/β-catenin signaling is highly conserved throughout metazoans, is required for numerous essential events in development, and serves as a stem cell niche signal in many contexts. Misregulation of the pathway is linked to several human pathologies, most notably cancer. Wnt stimulation results in stabilization and nuclear import of β-catenin, which then acts as a transcriptional co-activator. Transcription factors of the T-cell family (TCF) are the best-characterized nuclear binding partners of β-catenin and mediators of Wnt gene regulation. This review provides an update on what is known about the transcriptional activation of Wnt target genes, highlighting recent work that modifies the conventional model. Wnt/β-catenin signaling regulates genes in a highly context-dependent manner, and the role of other signaling pathways and TCF co-factors in this process will be discussed. Understanding Wnt gene regulation has served to elucidate many biological roles of the pathway, and we will use examples from stem cell biology, metabolism, and evolution to illustrate some of the rich Wnt biology that has been uncovered.
Highlights
The Wnt/β-catenin (Wnt/β-cat) pathway is conserved throughout metazoans and is essential for development and tissue homeostasis in adult organisms
The identification of Wnt transcriptional targets has enhanced our knowledge of the biological importance of Wnt/β-cat signaling
We will summarize recent findings on how the Wnt/β-cat pathway regulates transcription and provide examples of how identifying Wnt targets has broadened our knowledge of stem cell biology, the regulation of metabolism, and the evolution of physical traits
Summary
The Wnt/β-catenin (Wnt/β-cat) pathway is conserved throughout metazoans and is essential for development and tissue homeostasis in adult organisms (reviewed in 1–3). This study provides the clearest description to date of some of the chromatin events that tie the binding of TCF and β-cat to enhancers with the initiation of transcription at Wnt target loci, and it will be interesting to see if they are typical for Wnt gene activation beyond the human embryonic stem cells used in this report. Mouse embryonic stem cells lacking TCF3 have elevated FoxA2 expression and can differentiate into endoderm (albeit more slowly than normal) in the absence of Wnt stimulation[66] While this indicates that derepression of Wnt targets is a major driver for endoderm differentiation, another endoderm marker, Sox[17], is directly activated by TCF4/ TCF7L2 and β-cat[67]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
