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.
Highlights
GATA transcription factors typically function in concert with Friend of GATA (FOG) cofactors to regulate the formation of numerous cell types [1,2]
We examined the expression of GATA and FOG mRNAs in whole adult mouse livers by quantitative RT-PCR
chromatin immunoprecipitation (ChIP) followed by deep sequencing revealed that GATA4 occupies genes associated with liver specific functions
Summary
GATA transcription factors typically function in concert with Friend of GATA (FOG) cofactors to regulate the formation of numerous cell types [1,2]. FOG1 and FOG2 are multi-type zinc finger proteins that like GATA factors are expressed in a highly tissue-restricted fashion [1]. FOG proteins are unable to bind DNA directly and function entirely via association with the N-terminal zinc fingers of GATA factors [6,7]. Both GATA1 and FOG1 are essential for normal erythropoiesis [6,8,9,10] and megakaryopoiesis [11] in a manner dependent upon their direct physical interaction [12,13,14]. Direct contacts between GATA4 and FOG factors are required for the development of the heart and small intestine [15,16]
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