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HNF6 and Rev-erba Integrate Hepatic Lipid Metabolism By Overlapping and Distinct Transcriptional Mechanisms

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE83791 | GEO | 2016/06/29

SECONDARY ACCESSION(S): PRJNA327023

REPOSITORIES: GEO

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HNF6 and Rev-erba Integrate Hepatic Lipid Metabolism By Overlapping and Distinct Transcriptional Mechanisms

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-06-29 | E-GEOD-83791 | biostudies-arrayexpress

HNF6 and Rev-erbα integrate hepatic lipid metabolism by overlapping and distinct transcriptional mechanisms.

Project description:Hepatocyte nuclear factor 6 (HNF6) is required for liver development, but its role in adult liver metabolism is not known. Here we show that deletion of HNF6 in livers of adult C57Bl/6 mice leads to hepatic steatosis in mice fed normal laboratory chow. Although HNF6 is known mainly as a transcriptional activator, hepatic loss of HNF6 up-regulated many lipogenic genes bound directly by HNF6. Many of these genes are targets of the circadian nuclear receptor Rev-erbα, and binding of Rev-erbα at these sites was lost when HNF6 was ablated in the liver. While HNF6 and Rev-erbα coordinately regulate hepatic lipid metabolism, each factor also affects additional gene sets independently. These findings highlight a novel mechanism of transcriptional repression by HNF6 and demonstrate how overlapping and distinct mechanisms of transcription factor function contribute to the integrated physiology of the liver.

| S-EPMC4973293 | biostudies-literature

HNF6 and Rev-erba Integrate Hepatic Lipid Metabolism By Overlapping and Distinct Transcriptional Mechanisms [Affymetrix]

Project description:We address the function of HNF6 in the mouse liver metabolism and Rev-erba cistrome We performed microarray in mouse livers at 5pm of the day and compared between WT and HNF6-depleted livers.

2016-06-29 | E-GEOD-83789 | biostudies-arrayexpress

HNF6 and Rev-erba Integrate Hepatic Lipid Metabolism By Overlapping and Distinct Transcriptional Mechanisms [Affymetrix]

Project description:We address the function of HNF6 in the mouse liver metabolism and Rev-erba cistrome

2016-06-29 | GSE83789 | GEO

HNF6 and Rev-erba Integrate Hepatic Lipid Metabolism By Overlapping and Distinct Transcriptional Mechanisms [ChIP-Seq]

Project description:We address the function of HNF6 in the mouse liver metabolism and Rev-erba cistrome We performed Rev-erba ChIP-seq in mouse livers at 5pm of the day and compared between WT and HNF6-depleted livers.

2016-06-29 | E-GEOD-83790 | biostudies-arrayexpress

HNF6 and Rev-erba Integrate Hepatic Lipid Metabolism By Overlapping and Distinct Transcriptional Mechanisms [ChIP-Seq]

Project description:We address the function of HNF6 in the mouse liver metabolism and Rev-erba cistrome

2016-06-29 | GSE83790 | GEO

HNF6 and Rev-erba Integrate Hepatic Lipid Metabolism By Overlapping and Distinct Transcriptional Mechanisms

Project description:HNF6 and Rev-erba Integrate Hepatic Lipid Metabolism By Overlapping and Distinct Transcriptional Mechanisms

| PRJNA327023 | ENA

Discrete Functions of Rev-erba Couple Metabolism to the Clock

Project description:This SuperSeries is composed of the SubSeries listed below.

2015-06-16 | GSE67973 | GEO

Discrete Functions of Rev-erba Couple Metabolism to the Clock [array]

Project description:Circadian and metabolic physiology are intricately intertwined, as illustrated by Rev-erb , a transcription factor (TF) that functions both as a core repressive component of the cell autonomous clock and as a regulator of metabolic genes. Here we show that Rev-erb modulates the clock and metabolism by different genomic mechanisms. Clock control requires Rev-erb to bind directly to the genome at its cognate sites, where it competes with activating ROR TFs. By contrast, Rev-erb regulates metabolic genes primarily by recruiting the HDAC3 corepressor to sites to which it is tethered by cell type-specific transcription factors. Thus, direct competition between Rev-erb and ROR TFs provides a universal mechanism for self-sustained control of molecular clock across all tissues, whereas Rev-erb utilizes lineage-determining factors to convey a tissue-specific epigenomic rhythm that regulates metabolism tailored to the specific need of that tissue. Gene expressions in wild type and RORs depleted mouse livers were compared using Affymetrix MoGene2.0st array. Four biological replicates were used for each condition.

2015-06-16 | E-GEOD-67964 | biostudies-arrayexpress

Discrete Functions of Rev-erba Couple Metabolism to the Clock [HTS]

Project description:Circadian and metabolic physiology are intricately intertwined, as illustrated by Rev-erb , a transcription factor (TF) that functions both as a core repressive component of the cell autonomous clock and as a regulator of metabolic genes. Here we show that Rev-erb modulates the clock and metabolism by different genomic mechanisms. Clock control requires Rev-erb to bind directly to the genome at its cognate sites, where it competes with activating ROR TFs. By contrast, Rev-erb regulates metabolic genes primarily by recruiting the HDAC3 corepressor to sites to which it is tethered by cell type-specific transcription factors. Thus, direct competition between Rev-erb and ROR TFs provides a universal mechanism for self-sustained control of molecular clock across all tissues, whereas Rev-erb utilizes lineage-determining factors to convey a tissue-specific epigenomic rhythm that regulates metabolism tailored to the specific need of that tissue. Biological replicates were uploaded in separated files and indicated in the file names.

2015-06-16 | E-GEOD-67962 | biostudies-arrayexpress

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