PXD047767 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Identification of a chromatin-bound ERRα interactome network in mouse liver |
Description | 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. |
HostingRepository | PRIDE |
AnnounceDate | 2024-06-22 |
AnnouncementXML | Submission_2024-06-22_08:28:28.488.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Vincent Giguere |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | LTQ Orbitrap Velos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-12-12 15:07:06 | ID requested | |
⏵ 1 | 2024-06-22 08:28:29 | announced | |
Publication List
10.1016/j.molmet.2024.101925; |
Scholtes C, Dufour CR, Pleynet E, Kamyabiazar S, Hutton P, Baby R, Guluzian C, Gigu, è, re V, interactome network in mouse liver. Mol Metab, 83():101925(2024) [pubmed] |
Keyword List
submitter keyword: HCFC1 |
ERRα |
nuclear receptor |
RIME |
mitochondrial respiration |
OXPHOS. |
Contact List
Vincent Giguère |
contact affiliation | Goodman Cancer Institute, McGill University |
contact email | vincent.giguere@mcgill.ca |
lab head | |
Vincent Giguere |
contact affiliation | McGill University |
contact email | vincent.giguere@mcgill.ca |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD047767
- Label: PRIDE project
- Name: Identification of a chromatin-bound ERRα interactome network in mouse liver