Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-017-02786-5
Keywords
-
Categories
Funding
- CRUK [A19277]
- MRC
- Pancreatic Cancer UK
- Federal Agency for Scientific Organizations (FASO Russia) [0324-2016-0008]
- Wellcome Trust
- Science Foundation Ireland [15/CDA/3495]
- Cancer Research UK [19277, 23969] Funding Source: researchfish
- Medical Research Council [1477557, MC_PC_12002, 985361, 1383407] Funding Source: researchfish
- Pancreatic Cancer UK [FLF2015_06_Oxford] Funding Source: researchfish
- Science Foundation Ireland (SFI) [15/CDA/3495] Funding Source: Science Foundation Ireland (SFI)
- MRC [MC_PC_12002] Funding Source: UKRI
Ask authors/readers for more resources
Transition from pluripotency to differentiation is a pivotal yet poorly understood developmental step. Here, we show that the tumour suppressor RASSF1A is a key player driving the early specification of cell fate. RASSF1A acts as a natural barrier to stem cell self-renewal and iPS cell generation, by switching YAP from an integral component in the beta-catenin-TCF pluripotency network to a key factor that promotes differentiation. We demonstrate that epigenetic regulation of the Rassf1A promoter maintains stemness by allowing a quaternary association of YAP-TEAD and beta-catenin-TCF3 complexes on the Oct4 distal enhancer. However, during differentiation, promoter demethylation allows GATA1-mediated RASSF1A expression which prevents YAP from contributing to the TEAD/beta-catenin-TCF3 complex. Simultaneously, we find that RASSF1A promotes a YAP-p73 transcriptional programme that enables differentiation. Together, our findings demonstrate that RASSF1A mediates transcription factor selection of YAP in stem cells, thereby acting as a functional switch between pluripotency and initiation of differentiation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available