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Comparision of hepatic gene expression between fasted and fed ad lib states in C57B6J (WT) and CREBH KO mice

ABSTRACT: To determine hepatic gene expression changes in fasted state, we employed the microarray analysis. We collected the livers from 8-weeks-old male WT and CREBH KO mice in both fasted and fed ad lib states.

ORGANISM(S): Mus musculus

PROVIDER: GSE143420 | GEO | 2020/01/11

REPOSITORIES: GEO

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Comparision of hepatic gene expression between fasted and fed ad lib states in C57B6J (WT) and CREBH KO mice

Project description:Comparision of hepatic gene expression between fasted and fed ad lib states in C57B6J (WT) and CREBH KO mice

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Comparision of hepatic gene expression between HFHS diet-fed WT and CREBH-Tg mice

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Project description:Regulation of nutrient status during fasting and refeeding plays an important role in maintaining metabolic homeostasis in the liver. Thus, we investigated the impact of the physiological fed–fasted–refed cycle on hepatic gene expression in nutrient-sensitive mice. We performed transcriptomic analysis of liver samples in fed, fasted and refed groups of mice. Through mRNA-sequencing (RNA-Seq) and miRNA-Seq, we compared fasted and fed states (fasted versus fed cohort) as well as refed and fasted states (refed versus fasted cohort) to detect dynamic alterations of hepatic mRNA– miRNA expression during the fed–fasted–refed cycle

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Integrative genomic analysis of CREB defines a critical role for transcription factor networks in mediating the fed/fasted switch in liver [ChIP-seq]

Project description:Metabolic homeostasis in mammals critically depends on the regulation of fasting-induced genes by CREB in the liver. Previous genome-wide analysis has shown that only a small percentage of CREB target genes are induced in response to fasting-associated signaling pathways. The precise molecular mechanisms by which CREB specifically targets these genes in response to alternating hormonal cues remain to be elucidated. We performed chromatin immunoprecipitation coupled to high-throughput sequencing of CREB in livers from both fasted and re-fed mice. In order to quantitatively compare the extent of CREB-DNA interactions genome-wide between these two physiological conditions we developed a novel, robust analysis method, termed the M-bM-^@M-^Xsingle sample independenceM-bM-^@M-^Y (SSI) test that greatly reduced the number of false positive peaks. We found that CREB remains constitutively bound to its target genes in the liver regardless of the metabolic state. Integration of the CREB cistrome with expression microarrays of fasted and re-fed mouse livers and ChIP-seq data for additional transcription factors revealed that the gene expression switches between the fasted and fed states are associated with co-localization of additional transcription factors at CREB sites. Our results support a model in which CREB is constitutively bound to thousands of potential target genes and combinatorial interactions between DNA-binding factors are necessary to achieve the specific transcriptional response of the liver to fasting. Furthermore, our genome-wide analysis identifies thousands of novel CREB target genes in liver, including a previously unknown role for CREB in regulating ER stress genes in response to nutrient influx. CREB ChIP-seq was performed on mouse liver from fasted and re-fed mice, using 5 separate biological replicates for each condition. GR and C/EBP(beta) ChIP-seq were performed as single replicates on ad-lib fed mice.

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Expression data from the liver of wild-type and Cnot3+/- mice: Fed vs Fasted

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Global hepatic transcript data from fasted male BXD strains on chow or high fat diet

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Global hepatic transcript data from fasted male BXD strains on chow or high fat diet

Project description:Transcript data from livers from fasted-state BXD strains on chow or high fat diet We used microarrays to compare the hepatic expression differences across the BXD strain family and across two diverse diets 29-week-old male mice were fasted overnight (6pm-9am), anesthetized under isoflurane, and perfused, then livers were snap-frozen in liquid nitrogen for RNA extraction and RNEasy cleanup. Each dietary and strain cohort consisted of ~5 animals which were prepared independently then pooled evenly by M-BM-5g RNA before the Affymetrix arrays were run.

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