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| Status |
Public on Apr 17, 2024 |
| Title |
Identification of a chromatin-bound ERRα interactome network in mouse liver [ChIP-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Objective
Estrogen-related-receptor α (ERRα) plays a critical role in the transcriptional regulation of cellular bioenergetics and metabolism, and perturbations in its activity have been associated with metabolic diseases. While several coactivators and corepressors of ERRα have been identified to date, a knowledge gap remains in understanding the extent to which ERRα cooperates with coregulators in the control of gene expression. Herein, we mapped the primary chromatin-bound ERRα interactome in mouse liver.
Methods
RIME (Rapid Immuno-precipitation Mass spectrometry of Endogenous proteins) analysis using mouse liver samples from two circadian time points was used to catalog ERRα-interacting proteins on chromatin. The genomic crosstalk between ERRα and its identified cofactors in the transcriptional control of precise gene programs was explored through cross-examination of genome-wide binding profiles from chromatin immunoprecipitation-sequencing (ChIP-seq) studies. The dynamic interplay between ERRα and its newly uncovered cofactor Host cell factor C1 (HCFC1) was further investigated by loss-of-function studies in hepatocytes
Results
Characterization of the hepatic ERRα chromatin interactome led to the identification of 48 transcriptional interactors of which 42 were previously unknown including HCFC1. Interrogation of available ChIP-seq binding profiles highlighted oxidative phosphorylation (OXPHOS) under the control of a complex regulatory network between ERRα and multiple cofactors. While ERRα and HCFC1 were found to bind to a large set of common genes, only a small fraction showed their co-localization, found predominately near the transcriptional start sites of genes particularly enriched for components of the mitochondrial respiratory chain. Knockdown studies demonstrated inverse regulatory actions of ERRα and HCFC1 on OXPHOS gene expression ultimately dictating the impact of their loss-of-function on mitochondrial respiration.
Conclusions
Our work unveils a repertoire of previously unknown transcriptional partners of ERRα comprised of chromatin modifiers and transcription factors thus advancing our knowledge of how ERRα regulates metabolic transcriptional programs.
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| Overall design |
Chromatin immunoprecipitation followed by sequencing (ChIP-seq) for HCFC1 or IgG control was conducted in Hepa-6 cells treated with 200nM of siRNAs targeting ERRα (siERRa, siE), HCFC1 (siHCFC1, siH) or control siRNAs (siC) for 96h.
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| Contributor(s) |
Scholtes C, Giguère V, Dufour CR |
| Citation(s) |
38537884 |
| |
| Submission date |
Dec 12, 2023 |
| Last update date |
Apr 18, 2024 |
| Contact name |
Vincent Giguère |
| E-mail(s) |
vincent.giguere@mcgill.ca
|
| Phone |
514-398-5899
|
| Organization name |
McGill University
|
| Department |
Goodman Cancer Centre
|
| Street address |
1160 Pine Ave West, McIntyre Bldg Room 710
|
| City |
Montréal |
| State/province |
QC |
| ZIP/Postal code |
H3A 1A3 |
| Country |
Canada |
| |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE250045 |
Identification of a chromatin-bound ERRα interactome network in mouse liver |
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| Relations |
| BioProject |
PRJNA1051653 |
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