The Genomic Context and Corecruitment of SP1 Affect ERRα Coactivation by PGC-1α in Muscle Cells

Salatino, Silvia and Kupr, Barbara and Baresic, Mario and van Nimwegen, Erik and Handschin, Christoph. (2016) The Genomic Context and Corecruitment of SP1 Affect ERRα Coactivation by PGC-1α in Muscle Cells. Molecular Endocrinology, 30 (7). pp. 809-825.

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Official URL: http://edoc.unibas.ch/43519/

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The peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) coordinates the transcriptional network response to promote an improved endurance capacity in skeletal muscle, eg, by coactivating the estrogen-related receptor-α (ERRα) in the regulation of oxidative substrate metabolism. Despite a close functional relationship, the interaction between these 2 proteins has not been studied on a genomic level. We now mapped the genome-wide binding of ERRα to DNA in a skeletal muscle cell line with elevated PGC-1α and linked the DNA recruitment to global PGC-1α target gene regulation. We found that, surprisingly, ERRα coactivation by PGC-1α is only observed in the minority of all PGC-1α recruitment sites. Nevertheless, a majority of PGC-1α target gene expression is dependent on ERRα. Intriguingly, the interaction between these 2 proteins is controlled by the genomic context of response elements, in particular the relative GC and CpG content, monomeric and dimeric repeat-binding site configuration for ERRα, and adjacent recruitment of the transcription factor specificity protein 1. These findings thus not only reveal a novel insight into the regulatory network underlying muscle cell plasticity but also strongly link the genomic context of DNA-response elements to control transcription factor-coregulator interactions.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Associated Research Groups > Pharmakologie (Handschin)
05 Faculty of Science > Departement Biozentrum > Growth & Development > Growth & Development (Handschin)
UniBasel Contributors:Handschin, Christoph and van Nimwegen, Erik
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Endocrine Society
Note:Publication type according to Uni Basel Research Database: Journal article
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edoc DOI:
Last Modified:26 Oct 2017 12:07
Deposited On:18 Aug 2016 12:47

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