Hippo signaling influences HNF4A and FOXA2 enhancer switching during hepatocyte differentiation

Olivia Alder, Rebecca Cullum, Sam Lee, Arohumam C. Kan, Wei Wei, Yuyin Yi, Victoria C. Garside, Misha Bilenky, Malachi Griffith, A. Sorana Morrissy, Gordon A. Robertson, Nina Thiessen, Yongjun Zhao, Qian Chen, Duojia Pan, Steven J M Jones, Marco A. Marra, Pamela A. Hoodless

Research output: Contribution to journalArticlepeer-review

Abstract

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 invivo 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.

Original languageEnglish (US)
Pages (from-to)261-271
Number of pages11
JournalCell Reports
Volume9
Issue number1
DOIs
StatePublished - Oct 9 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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