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PLoS One. 2013 Dec 18;8(12):e83723. doi: 10.1371/journal.pone.0083723. eCollection 2013.

Function of GATA factors in the adult mouse liver.

Author information

1
Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America ; Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
2
Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, Pennsylvania, United States of America.
3
Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
4
Division of Transplant Immunology, Department of Pathology and Laboratory Medicine and Biesecker Center for Pediatric Liver Disease, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
5
Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
6
Division of Gastroenterology, Department of Medicine, Department of Cell and Developmental Biology and Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
7
Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania, United States of America.

Abstract

GATA transcription factors and their Friend of Gata (FOG) cofactors control the development of diverse tissues. GATA4 and GATA6 are essential for the expansion of the embryonic liver bud, but their expression patterns and functions in the adult liver are unclear. We characterized the expression of GATA and FOG factors in whole mouse liver and purified hepatocytes. GATA4, GATA6, and FOG1 are the most prominently expressed family members in whole liver and hepatocytes. GATA4 chromatin immunoprecipitation followed by high throughput sequencing (ChIP-seq) identified 4409 occupied sites, associated with genes enriched in ontologies related to liver function, including lipid and glucose metabolism. However, hepatocyte-specific excision of Gata4 had little impact on gross liver architecture and function, even under conditions of regenerative stress, and, despite the large number of GATA4 occupied genes, resulted in relatively few changes in gene expression. To address possible redundancy between GATA4 and GATA6, both factors were conditionally excised. Surprisingly, combined Gata4,6 loss did not exacerbate the phenotype resulting from Gata4 loss alone. This points to the presence of an unusually robust transcriptional network in adult hepatocytes that ensures the maintenance of liver function.

PMID:
24367609
PMCID:
PMC3867416
DOI:
10.1371/journal.pone.0083723
[Indexed for MEDLINE]
Free PMC Article

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