Format

Send to

Choose Destination
Cell Rep. 2014 Oct 9;9(1):261-271. doi: 10.1016/j.celrep.2014.08.046. Epub 2014 Sep 25.

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

Author information

1
Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC V5Z1L3, Canada.
2
Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z1L3, Canada.
3
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
4
Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z1L3, Canada; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC V5A1S6, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, BC V5Z4H4, Canada.
5
Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z1L3, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, BC V5Z4H4, Canada.
6
Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC V5Z1L3, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, BC V5Z4H4, Canada. Electronic address: hoodless@bccrc.ca.

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 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.

PMID:
25263553
PMCID:
PMC4612615
DOI:
10.1016/j.celrep.2014.08.046
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center