title: The Genomic Context and Corecruitment of SP1 Affect ERRα Coactivation by PGC-1α in Muscle Cells.
abstract: 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.
authors.affiliation: Focal Area Growth and Development (S.S., B.K., M.B., C.H.) and Focal Area Computational and Systems Biology (S.S., E.N.), Biozentrum, University of Basel, and Swiss Institute of Bioinformatics (S.S., E.N.), CH-4056 Basel, Switzerland.
authors.forename: Silvia
authors.initials: S
authors.lastname: Salatino
authors.affiliation: Focal Area Growth and Development (S.S., B.K., M.B., C.H.) and Focal Area Computational and Systems Biology (S.S., E.N.), Biozentrum, University of Basel, and Swiss Institute of Bioinformatics (S.S., E.N.), CH-4056 Basel, Switzerland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Kupr
authors.affiliation: Focal Area Growth and Development (S.S., B.K., M.B., C.H.) and Focal Area Computational and Systems Biology (S.S., E.N.), Biozentrum, University of Basel, and Swiss Institute of Bioinformatics (S.S., E.N.), CH-4056 Basel, Switzerland.
authors.forename: Mario
authors.initials: M
authors.lastname: Baresic
authors.forename: Saeed
authors.initials: S
authors.lastname: Omidi
authors.affiliation: Focal Area Growth and Development (S.S., B.K., M.B., C.H.) and Focal Area Computational and Systems Biology (S.S., E.N.), Biozentrum, University of Basel, and Swiss Institute of Bioinformatics (S.S., E.N.), CH-4056 Basel, Switzerland.
authors.forename: Erik
authors.initials: E
authors.lastname: van Nimwegen
authors.affiliation: Focal Area Growth and Development (S.S., B.K., M.B., C.H.) and Focal Area Computational and Systems Biology (S.S., E.N.), Biozentrum, University of Basel, and Swiss Institute of Bioinformatics (S.S., E.N.), CH-4056 Basel, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Handschin
mesh_terms: D000818:Animals; D001482:Base Composition / Q000235:genetics; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D018899:CpG Islands / Q000235:genetics; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics / Q000378:metabolism*; D025341:Principal Component Analysis; D034741:RNA, Small Interfering / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D034741:RNA, Small Interfering; D011960:Receptors, Estrogen; D016329:Sp1 Transcription Factor; D000097983:ERRalpha Estrogen-Related Receptor; C485290:Ppargc1a protein, mouse