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Series GSE200658 Query DataSets for GSE200658
Status Public on Apr 01, 2024
Title The nuclear receptors ERRα and PPARα co-ordinately control starvation-induced gene expression in hepatocytes.
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Peroxisome-proliferator activated receptor α (PPARα) activation reprograms liver gene expression to support fatty acid oxidation during fasting. How PPARα engages in transcriptional programs coping with catabolic fasting responses is insufficiently understood. By applying a protein-protein interaction methodology that also captures transient interactions, we revealed the orphan nuclear receptor estrogen-related receptor α (ERRα) as a novel interaction partner of liganded PPARα and found that this interaction is enhanced following cellular nutrient starvation. Among target genes affected by PPARα-ERRα transcriptional crosstalk in fasted murine livers, multiple components of the electron transport chain were identified. Using pharmacological tools to study hepatic gene subsets under dual PPARα and ERRα control and moving from short-term to prolonged nutrient deprivation, we found that ERRα can switch from being a PPARα target gene suppressor to a marked PPARα target gene activator. Mechanistically, ERRα may control PPARα transcriptional activity via binding onto PPARα’s coactivator interaction site and via facilitating cofactor relays. In sum, a variety of crosstalk mechanisms between PPARα and ERRα seems to co-ordinately drive essential gene regulatory changes in the starving hepatocyte.
Overall design The transcriptomic signature underlying the ERRα and PPARα crosstalk in murine hepatocytes using RNA-sequencing of the following conditions: DMSO, PPARα-specific agonist GW7647 (GW), ERRα inverse agonist Compound 29 (C29), GW+C29.
Contributor(s) Desmet SJ, Thommis J, Li Y, de Vries RM, Timmermans S, Fijalkowska D, Ratman D, Van Hamme E, De Cauwer L, Libert C, Staels B, Brunsveld L, Peelman F, Tavernier J, De Bosscher K
Citation(s) 38631478
Submission date Apr 12, 2022
Last update date Jul 01, 2024
Contact name Karolien De Bosscher
Organization name VIB-UGent Center for Medical Biotechnology
Street address Technologiepark-Zwijnaarde 75
City Gent
ZIP/Postal code 9052
Country Belgium
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (12)
GSM6040931 primary murine hepatocytes, GW, rep1
GSM6040932 primary murine hepatocytes, GW, rep2
GSM6040933 primary murine hepatocytes, GW, rep3
BioProject PRJNA825730

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Supplementary file Size Download File type/resource
GSE200658_RAW.tar 20.2 Mb (http)(custom) TAR (of TSV)
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Raw data are available in SRA
Processed data provided as supplementary file

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