Tead proteins activate the Foxa2 enhancer in the node in cooperation with a second factor
2005
The cell population and the activity of the organizer change during the
course of development. We addressed the mechanism of mouse node development
via an analysis of the node/notochord enhancer (NE) of Foxa2 . We
first identified the core element (CE) of the enhancer, which in multimeric
form drives gene expression in the node. The CE was activated in
Wnt/β-catenin-treated P19 cells with a time lag, and this activation was
dependent on two separate sequence motifs within the CE. These same motifs
were also required for enhancer activity in transgenic embryos. We identified
the Tead family of transcription factors as binding proteins for the 3′
motif. Teads and their co-factor YAP65 activated the CE in P19 cells, and
binding of Tead to CE was essential for enhancer activity. Inhibition of Tead
activity by repressor-modified Tead compromised NE enhancer activation and
notochord development in transgenic mouse embryos. Furthermore, manipulation
of Tead activity in zebrafish embryos led to altered expression of
foxa2 in the embryonic shield. These results suggest that Tead
activates the Foxa2 enhancer core element in the mouse node in
cooperation with a second factor that binds to the 5′ element, and that
a similar mechanism also operates in the zebrafish shield.
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