Tead proteins activate the Foxa2 enhancer in the node in cooperation with a second factor.
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/beta-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.
Sawada
Atsushi
A
Laboratory for Embryonic Induction, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Kobe, Hyogo 650-0047, Japan.
Nishizaki
Yuriko
Y
Sato
Hiroko
H
Yada
Yukari
Y
Nakayama
Rika
R
Yamamoto
Shinji
S
Nishioka
Noriyuki
N
Kondoh
Hisato
H
Sasaki
Hiroshi
H
D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology*; D004622:Embryo, Mammalian; D004625:Embryo, Nonmammalian; D004742:Enhancer Elements, Genetic; D051858:Forkhead Transcription Factors / Q000502:physiology; D051542:Hepatocyte Nuclear Factor 3-beta / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009672:Notochord / Q000378:metabolism*; D009687:Nuclear Proteins / Q000502:physiology*; D020897:Organizers, Embryonic / Q000254:growth & development; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000502:physiology*; D051153:Wnt Proteins / Q000502:physiology; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000502:physiology*
D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C496503:Foxa2 protein, mouse; D009687:Nuclear Proteins; D000091262:TEA Domain Transcription Factors; C083215:Tead1 protein, mouse; D014157:Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C082243:foxa2 protein, zebrafish; C506512:tead1a protein, zebrafish; D051542:Hepatocyte Nuclear Factor 3-beta