Epigenetic mechanisms that define the exit from pluripotency
Final Report Abstract
The aim of this work was to characterize the transcriptional and epigenetic changes that coincide with exit from pluripotency in an endoderm differentiation system. We found that expression of a key mes-endoderm transcription factor, Foxa2, coincides with loss of pluripotency in vivo. We then characterized the transcriptional changes upon pluripotency exit and identified > 1000 coding genes to be differentially regulated, while non-coding RNA transcriptional regulation as comparably mild. We also determined epigenetic changes upon exit from pluripotency and identified a large number of stage-specificenhancers that are likely to mediate the transcriptional changes. ChIP-seq profiling of major transcription factors revealed that targets of the pluripotency network and the endoderm network hardly overlap. Thus our data suggest that the switch in signaling from Lif/Bmp4 to Wnt/Activin results in activation of key endoderm transcription factors which establish the endoderm network, while maintenance of the pluripotency network is comprimized. Until the end of the funding period we are going to investigate the impact of DNA methylation/hydroxymethylation on pluripotency exit.
Publications
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Dynamic changes of the epigeneticlandscape during cellular differentiation. Epigenomics. 2013 Dec;5(6):701-13
Dambacher S, de Almeida GP, Schotta G
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Wnt/β-catenin signalling regulates Sox17 expression and is essential for organizer and endoderm formation in the mouse. Development. 2013 Aug; 140(15):3128-38
Engert S, Burtscher I, Liao WP, Dulev S, Schotta G, Lickert H
