Identification of a chromatin-bound ERRα interactome network in mouse liver

Scholtes, Charlotte; Dufour, Catherine Rosa; Pleynet, Emma; Kamyabiazar, Samaneh; Hutton, Phillipe; Baby, Reeba; Guluzian, Christina; Giguère, Vincent

doi:10.1016/j.molmet.2024.101925

Molecular Metabolism

2024

DOI: 10.1016/j.molmet.2024.101925

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Identification of a chromatin-bound ERRα interactome network in mouse liver

Charlotte Scholtes,

Catherine Rosa Dufour,

Emma Pleynet

et al.

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2024

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Cited by 2 publications

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TheDrosophilaEstrogen-Related Receptor promotes triglyceride storage within the larval fat body

Fasteen,

Hernandez,

Policastro

et al. 2024

Preprint

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The Estrogen-Related Receptor (ERR) family of nuclear receptors (NRs) serve key roles in coordinating triglyceride (TAG) accumulation with juvenile growth and development. In both insects and mammals, ERR activity promotes TAG storage during the post-embryonic growth phase, with loss-of-function mutations in mouseEsrraandDrosophila melanogaster dERRinducing a lean phenotype. However, the role of insect ERRs in controlling TAG accumulation within adipose tissue remains poorly understood, as previous transcriptomic and metabolomic studies relied on whole animal analyses. Here we address this shortcoming by using tissue-specific approaches to examine the role of dERR in regulating lipid metabolism within theDrosophilalarval fat body. We find that dERR autonomously promotes TAG accumulation within fat body cells and regulates expression of genes involved in glycolysis, β-oxidation, and mevalonate metabolism. As an extension of these results, we not only discovered thatdERRmutant fat bodies exhibit decreased expression of known dHNF4 target genes but also found that dHNF4 activity is decreased indERRmutants. Overall, our findings indicate that dERR plays a multifaceted role in the larval fat body to coordinate lipid storage with developmental growth and hint at a conserved mechanism by which ERR and HNF4 homologs coordinately regulate metabolic gene expression.

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TheDrosophilaEstrogen-Related Receptor promotes triglyceride storage within the larval fat body

Fasteen,

Hernandez,

Policastro

et al. 2024

Preprint

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An ERRα-ZEB1 transcriptional signature predicts survival in triple-negative breast cancers

Shi,

Poulard,

Cerutti

et al. 2024

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Background. Transcription factors (TFs) act together with co-regulators to modulate the expression of their target genes, which eventually dictates their pathophysiological effects. Depending on the co-regulator, TFs can exert different activities. The Estrogen Related Receptor α (ERRα) acts as a transcription factor that regulates several pathophysiological phenomena. In particular, interactions with PGC-1 co-activators are responsible for the metabolic activities of ERRα. In breast cancers, ERRα exerts several tumor-promoting, metabolism-unrelated activities that do not depend on PGC1, questioning the identity of the co-activators involved in these cancer-related effects. Methods. We used bio-computing methods to identify potential co-factors that could be responsible for the activities of ERRα in cancer progression. Experimental validations were conducted in different breast cancer cell lines, using determination of mRNA expression, ChIP-qPCR and proximity ligation assays. Results. ZEB1 is proposed as a major ERRα co-factor that could be responsible for the expression of direct ERRα targets in triple-negative breast cancers (TNBC). We establish that ERRα and ZEB1 interact together and are bound to the promoters of their target genes that they transcriptionally regulate. Our further analyses show that the ERRα-ZEB1 downstream signature can predict the survival of the TNBC patients. Conclusions. The ERRα-ZEB1 complex is a major actor in breast cancer progression and expression of its downstream transcriptional targets can predict the overall survival of triple-negative breast cancer patients.

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Identification of a chromatin-bound ERRα interactome network in mouse liver

Cited by 2 publications

References 58 publications

TheDrosophilaEstrogen-Related Receptor promotes triglyceride storage within the larval fat body

TheDrosophilaEstrogen-Related Receptor promotes triglyceride storage within the larval fat body

An ERRα-ZEB1 transcriptional signature predicts survival in triple-negative breast cancers

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