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Series GSE173723 Query DataSets for GSE173723
Status Public on Sep 08, 2021
Title Impaired GR expression in liver disrupts feeding induced gene expression, glucose uptake and glycogen storage
Organisms Mus musculus; Rattus norvegicus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary The transition from a fasted to a fed state is associated with extensive transcriptional remodeling in hepatocytes facilitated by hormonal- and nutritional-regulated transcription factors. Here, we use a liver-specific glucocorticoid receptor (GR) knock-out (L-GRKO) model and primary hepatocytes to investigate the temporal expression of GR target genes in response to feeding. Interestingly, in addition to the well described fasting-regulated genes, we identify a subset of hepatic feeding-induced genes that requires GR for full expression, adding new insights to hepatic GR function. The GR-controlled feeding-induced genes include Gck encoding the glucokinase, which is important for hepatic glucose uptake, utilization and storage. We show that insulin and glucocorticoids cooperatively regulate Gck expression in primary hepatocytes in a GR-dependent manner. ChIP-seq experiments suggest direct GR regulation of Gck by GR occupancy of the promoter and two putative regulatory regions near the Gck gene (Gck -1kb and Gck -4.6kb). Enhancer-reporter assays and CRISPRi suggest that the 4.6kb upstream GR binding site is a functional Gck enhancer. L-GRKO blunts preprandial and early postprandial Gck expression and GR disruption ultimately affects early postprandial hepatic glucose uptake, phosphorylation and glycogen storage. Collectively, our study demonstrates how GR is positively involved in the hepatic feeding response exemplified in the direct regulation of the feeding-induced transcription of glucokinase, important for hepatic glucose metabolism.
Overall design Examination of feeding regulated gene expression in liver from C57BL/6 WT and liver specific GR KO mice. Analysis of dex and insulin mediated gene expression in primary hepatocytes
Contributor(s) Grøntved L, Præstholm S
Citation(s) 34731602
Submission date May 03, 2021
Last update date Nov 10, 2021
Contact name Lars Grøntved
Phone +45 24 60 14 06
Organization name University of Southern Denmark
Department Biochemistry and Molecular Biology
Street address Campusvej 55
City Odense
ZIP/Postal code 5230
Country Denmark
Platforms (3)
GPL18404 Illumina HiSeq 1500 (Rattus norvegicus)
GPL18480 Illumina HiSeq 1500 (Mus musculus)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (79)
GSM5277385 GFP_ZT10_r1
GSM5277386 GFP_ZT10_r2
GSM5277387 GFP_ZT10_r3
BioProject PRJNA726880
SRA SRP318197

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Supplementary file Size Download File type/resource
GSE173723_RAW.tar 161.1 Mb (http)(custom) TAR (of BEDGRAPH, TXT)
GSE173723_RNAseq_RAW_CT_FED_FAST.txt.gz 1.5 Mb (ftp)(http) TXT
GSE173723_RNAseq_RAW_CT_GFP_CRE.txt.gz 2.0 Mb (ftp)(http) TXT
GSE173723_RNAseq_RAW_CT_rat_hepa.txt.gz 342.9 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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