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GEO help: Mouse over screen elements for information. |
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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
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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.
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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.
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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 |
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Submission date |
Apr 12, 2022 |
Last update date |
Jul 01, 2024 |
Contact name |
Karolien De Bosscher |
E-mail(s) |
karolien.debosscher@vib-ugent.be
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Organization name |
VIB-UGent Center for Medical Biotechnology
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Street address |
Technologiepark-Zwijnaarde 75
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City |
Gent |
ZIP/Postal code |
9052 |
Country |
Belgium |
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Platforms (1) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (12)
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GSM6040934 |
primary murine hepatocytes, GW+C29, rep1 |
GSM6040935 |
primary murine hepatocytes, GW+C29, rep2 |
GSM6040936 |
primary murine hepatocytes, GW+C29, rep3 |
GSM6040937 |
primary murine hepatocytes, DMSO, rep1 |
GSM6040938 |
primary murine hepatocytes, DMSO, rep2 |
GSM6040939 |
primary murine hepatocytes, DMSO, rep3 |
GSM6040940 |
primary murine hepatocytes, C29, rep1 |
GSM6040941 |
primary murine hepatocytes, C29, rep2 |
GSM6040942 |
primary murine hepatocytes, C29, rep3 |
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Relations |
BioProject |
PRJNA825730 |
Supplementary file |
Size |
Download |
File type/resource |
GSE200658_RAW.tar |
20.2 Mb |
(http)(custom) |
TAR (of TSV) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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