PXD047767

PXD047767 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-12 15:07:06	ID requested
⏵ 1	2024-06-22 08:28:29	announced

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]

submitter keyword: HCFC1

ERRα

nuclear receptor

RIME

mitochondrial respiration

OXPHOS.

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

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PRIDE project URI

• PRIDE
  1. PXD047767
     1. Label: PRIDE project
     2. Name: Identification of a chromatin-bound ERRα interactome network in mouse liver