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Publication : Hippo signaling influences HNF4A and FOXA2 enhancer switching during hepatocyte differentiation.

First Author  Alder O Year  2014
Journal  Cell Rep Volume  9
Issue  1 Pages  261-271
PubMed ID  25263553 Mgi Jnum  J:323555
Mgi Id  MGI:6837528 Doi  10.1016/j.celrep.2014.08.046
Citation  Alder O, et al. (2014) Hippo signaling influences HNF4A and FOXA2 enhancer switching during hepatocyte differentiation. Cell Rep 9(1):261-271
abstractText  Cell fate acquisition is heavily influenced by direct interactions between master regulators and tissue-specific enhancers. However, it remains unclear how lineage-specifying transcription factors, which are often expressed in both progenitor and mature cell populations, influence cell differentiation. Using in vivo mouse liver development as a model, we identified thousands of enhancers that are bound by the master regulators HNF4A and FOXA2 in a differentiation-dependent manner, subject to chromatin remodeling, and associated with differentially expressed target genes. Enhancers exclusively occupied in the embryo were found to be responsive to developmentally regulated TEAD2 and coactivator YAP1. Our data suggest that Hippo signaling may affect hepatocyte differentiation by influencing HNF4A and FOXA2 interactions with temporal enhancers. In summary, transcription factor-enhancer interactions are not only tissue specific but also differentiation dependent, which is an important consideration for researchers studying cancer biology or mammalian development and/or using transformed cell lines.
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