Hippo Signaling Influences HNF4A and FOXA2 Enhancer Switching during Hepatocyte Differentiation

被引：98

作者：

Alder, Olivia ^{[1
]}

Cullum, Rebecca ^{[1
]}

Lee, Sam ^{[1
]}

Kan, Arohumam C. ^{[1
]}

Wei, Wei ^{[1
]}

Yi, Yuyin ^{[1
]}

Garside, Victoria C. ^{[1
]}

Bilenky, Misha ^{[2
]}

Griffith, Malachi ^{[2
]}

Morrissy, A. Sorana ^{[2
]}

Robertson, Gordon A. ^{[2
]}

Thiessen, Nina ^{[2
]}

Zhao, Yongjun ^{[2
]}

Chen, Qian ^{[3
]}

Pan, Duojia ^{[3
]}

Jones, Steven J. M. ^{[2
,4
,5
]}

Marra, Marco A. ^{[2
,5
]}

Hoodless, Pamela A. ^{[1
,5
]}

机构：

[1] British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada

[2] British Columbia Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada

[3] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA

[4] Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada

[5] Univ British Columbia, Dept Med Genet, Vancouver, BC V5Z 4H4, Canada

来源：

CELL REPORTS | 2014年 / 9卷 / 01期

关键词：

LIVER DEVELOPMENT; GENE-EXPRESSION; TRANSCRIPTION; PROTEIN; FIBROBLASTS; TOOL; IDENTIFICATION; PROLIFERATION; OCCUPANCY; CELLS;

D O I：

10.1016/j.celrep.2014.08.046

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：261 / 271

页数：11

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