⮝ Full datasets listing

PXD047767

PXD047767 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleIdentification of a chromatin-bound ERRα interactome network in mouse liver
DescriptionObjective 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.
HostingRepositoryPRIDE
AnnounceDate2024-06-22
AnnouncementXMLSubmission_2024-06-22_08:28:28.488.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterVincent Giguere
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListphosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentLTQ Orbitrap Velos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-12-12 15:07:06ID requested
12024-06-22 08:28:29announced
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 affiliationGoodman Cancer Institute, McGill University
contact emailvincent.giguere@mcgill.ca
lab head
Vincent Giguere
contact affiliationMcGill University
contact emailvincent.giguere@mcgill.ca
dataset submitter
Full Dataset Link List
Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/06/PXD047767
PRIDE project URI
Repository Record List
[ + ]