Hepatic nuclear factor 3 is an accessory factor required for the stimulation of phosphoenolpyruvate carboxykinase gene transcription by glucocorticoids

Wang, Jen-Chywan

doi:10.1210/me.10.7.794

Cited by 36 publications

(15 citation statements)

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“…They showed that mutation of the FoxA binding site in a promoter-reporter construct severely attenuated gene activation by glucocorticoids. A similar situation was shown to exist for another fasting-activated gene, Pck1 , by Daryl Granner’s group [41–43]. …”

Section: Foxa Factors and Nuclear Receptorssupporting

confidence: 59%

The FoxA factors in organogenesis and differentiation

Kaestner

2010

Current Opinion in Genetics & Development

174

160

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SummaryThe genetic analysis of the Foxa genes in both total and conditional mutant mice has clearly established that organogenesis of multiple systems is controlled by this subfamily of winged helix transcription factors. These discoveries followed the establishment of the conceptional framework of the mechanism of action of the FoxA proteins as "pioneer factors" that can engage chromatin before other transcription factors. Recent molecular and genomic studies have also shown that FoxA proteins can facilitate binding of several nuclear receptors to their respective targets in a contextdependent manner, greatly increasing the range and importance of FoxA factors in biology.

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Section: Foxa Factors and Nuclear Receptorssupporting

confidence: 59%

The FoxA factors in organogenesis and differentiation

Kaestner

2010

Current Opinion in Genetics & Development

174

160

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“…2D). C/EBP and HNF3alpha, two families of transcription factors whose binding motifs are highly represented in GBRs of glucocorticoid-activated genes, were previously shown to act with GR to participate in glucocorticoid-activate gene transcription [59], [60], [61], [62]. The HNF3alpha binding motif is similar to those of the FOX family transcription factors.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Analysis of Glucocorticoid Receptor Binding Regions in Adipocytes Reveal Gene Network Involved in Triglyceride Homeostasis

et al. 2010

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Glucocorticoids play important roles in the regulation of distinct aspects of adipocyte biology. Excess glucocorticoids in adipocytes are associated with metabolic disorders, including central obesity, insulin resistance and dyslipidemia. To understand the mechanisms underlying the glucocorticoid action in adipocytes, we used chromatin immunoprecipitation sequencing to isolate genome-wide glucocorticoid receptor (GR) binding regions (GBRs) in 3T3-L1 adipocytes. Furthermore, gene expression analyses were used to identify genes that were regulated by glucocorticoids. Overall, 274 glucocorticoid-regulated genes contain or locate nearby GBR. We found that many GBRs were located in or nearby genes involved in triglyceride (TG) synthesis (Scd-1, 2, 3, GPAT3, GPAT4, Agpat2, Lpin1), lipolysis (Lipe, Mgll), lipid transport (Cd36, Lrp-1, Vldlr, Slc27a2) and storage (S3-12). Gene expression analysis showed that except for Scd-3, the other 13 genes were induced in mouse inguinal fat upon 4-day glucocorticoid treatment. Reporter gene assays showed that except Agpat2, the other 12 glucocorticoid-regulated genes contain at least one GBR that can mediate hormone response. In agreement with the fact that glucocorticoids activated genes in both TG biosynthetic and lipolytic pathways, we confirmed that 4-day glucocorticoid treatment increased TG synthesis and lipolysis concomitantly in inguinal fat. Notably, we found that 9 of these 12 genes were induced in transgenic mice that have constant elevated plasma glucocorticoid levels. These results suggested that a similar mechanism was used to regulate TG homeostasis during chronic glucocorticoid treatment. In summary, our studies have identified molecular components in a glucocorticoid-controlled gene network involved in the regulation of TG homeostasis in adipocytes. Understanding the regulation of this gene network should provide important insight for future therapeutic developments for metabolic diseases.

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“…Indeed, FoxO1 and FoxA2 play roles in hepatic glucose homeostasis by controlling gluconeogenic gene expression (3,4,37,39). Additionally, both transcription factors have been shown to be involved in lipid metabolism.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide analysis of FoxO1 binding in hepatic chromatin: Potential involvement of FoxO1 in linking retinoid signaling to hepatic gluconeogenesis

Shin

Joshi

Hong

et al. 2012

Nucleic Acids Research

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The forkhead transcription factor FoxO1 is a critical regulator of hepatic glucose and lipid metabolism, and dysregulation of FoxO1 function has been implicated in diabetes and insulin resistance. We globally identified FoxO1 occupancy in mouse hepatic chromatin on a genome-wide level by chromatin immunoprecipitation coupled with high-throughput DNA sequencing (ChIP-seq). To establish the specific functional significance of FoxO1 against other FoxO proteins, ChIP-seq was performed with chromatin from liver-specific FoxO1 knockout and wild-type mice. Here we identified 401 genome-wide FoxO1-binding locations. Motif search reveals a sequence element, 5′ GTAAACA 3′, consistent with a previously known FoxO1-binding site. Gene set enrichment analysis shows that the data from FoxO1 ChIP-seq are highly correlated with the global expression profiling of genes regulated by FoxO1, demonstrating the functional relevance of our FoxO1 ChIP-seq study. Interestingly, gene ontology analysis reveals the functional significance of FoxO1 in retinoid metabolic processes. We show here that FoxO1 directly binds to the genomic sites for the genes in retinoid metabolism. Notably, deletion of FoxO1 caused a significantly reduced induction of Pck1 and Pdk4 in response to retinoids. As Pck1 and Pdk4 are downstream targets of retinoid signaling, these results suggest that FoxO1 plays a potential role in linking retinoid metabolism to hepatic gluconeogenesis.

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Hepatic nuclear factor 3 is an accessory factor required for the stimulation of phosphoenolpyruvate carboxykinase gene transcription by glucocorticoids

Cited by 36 publications

References 0 publications

The FoxA factors in organogenesis and differentiation

The FoxA factors in organogenesis and differentiation

Genome-Wide Analysis of Glucocorticoid Receptor Binding Regions in Adipocytes Reveal Gene Network Involved in Triglyceride Homeostasis

Genome-wide analysis of FoxO1 binding in hepatic chromatin: Potential involvement of FoxO1 in linking retinoid signaling to hepatic gluconeogenesis

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