E-MTAB-3061 - TEAD and YAP regulate the enhancer network of human embryonic pancreatic progenitors
Submitted on 30 November 2011, last updated on 17 March 2015, released on 6 April 2015
The genomic regulatory programs that underlie human organogenesis are poorly understood. Human pancreas development, in particular, has pivotal implications for pancreatic regeneration, cancer, and diabetes. We have now created maps of transcripts, active enhancers, and transcription factor networks in pancreatic multipotent progenitors obtained from human embryos, or derived in vitro from human embryonic stem cells. This revealed that artificial progenitors recapitulate salient transcriptional and epigenomic features of their natural counterparts. Using this resource, we show that TEAD1, a transcription factor controlled by Hippo signaling, is a core component of the combinatorial code of pancreatic progenitor enhancers. TEAD thus activates genes encoding regulators of signaling pathways and stage-specific transcription factors that are essential for normal pancreas development. Accordingly, chemical and genetic perturbations of TEAD and its coactivator YAP inhibited expression of known regulators such as FGFR2 and SOX9, and suppressed the proliferation and expansion of mouse and zebrafish pancreatic progenitors. These findings provide a resource of active enhancers and transcripts in human pancreatic multipotent progenitors, and uncover a central role of TEAD and YAP as signal-responsive regulators of the transcriptional program of early pancreas development.
ChIP-seq, RNA-seq of coding RNA, binding site identification design, development or differentiation design
TEAD and YAP regulate the enhancer network of human embryonic pancreatic progenitors. Cebola I, Rodríguez-Seguí SA, Cho CH, Bessa J, Rovira M, Luengo M, Chhatriwala M, Berry A, Ponsa-Cobas J, Maestro MA, Jennings RE, Pasquali L, Morán I, Castro N, Hanley NA, Gomez-Skarmeta JL, Vallier L, Ferrer J. :615-626 (2015), PMID:25915126
TEAD and YAP regulate the enhancer network of human embryonic pancreatic progenitors. Inês Cebola, Santiago A. Rodríguez-Seguí, Candy H.-H. Cho, JoséBessa, Meritxell Rovira, Mario Luengo, Mariya Chhatriwala, Andrew Berry, Joan Ponsa-Cobas, Miguel Angel Maestro, Rachel E. Jennings, Lorenzo Pasquali, Ignasi Morán, Natalia Castro, Neil A. Hanley, Jose Luis Gomez-Skarmeta, Ludovic Vallier and Jorge Ferrer.