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dc.contributor.authorLee, Heekyoungen_US
dc.contributor.authorQian, Kunen_US
dc.contributor.authorvon Toerne, Christineen_US
dc.contributor.authorHoerburger, Lenaen_US
dc.contributor.authorClaussnitzer, Melinaen_US
dc.contributor.authorHoffmann, Christophen_US
dc.contributor.authorGlunk, Viktoriaen_US
dc.contributor.authorWahl, Simoneen_US
dc.contributor.authorBreier, Michaelaen_US
dc.contributor.authorEck, Franziskaen_US
dc.contributor.authorJafari, Leilien_US
dc.contributor.authorMolnos, Sophieen_US
dc.contributor.authorGrallert, Haralden_US
dc.contributor.authorDahlman, Ingriden_US
dc.contributor.authorArner, Peteren_US
dc.contributor.authorBrunner, Corneliaen_US
dc.contributor.authorHauner, Hansen_US
dc.contributor.authorHauck, Stefanie M.en_US
dc.contributor.authorLaumen, Helmuten_US
dc.date.accessioned2017-05-01T19:27:40Z
dc.date.issued2017en_US
dc.identifier.citationLee, H., K. Qian, C. von Toerne, L. Hoerburger, M. Claussnitzer, C. Hoffmann, V. Glunk, et al. 2017. “Allele-specific quantitative proteomics unravels molecular mechanisms modulated by cis-regulatory PPARG locus variation.” Nucleic Acids Research 45 (6): 3266-3279. doi:10.1093/nar/gkx105. http://dx.doi.org/10.1093/nar/gkx105.en
dc.identifier.issnen
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:32630617
dc.description.abstractAbstract Genome-wide association studies identified numerous disease risk loci. Delineating molecular mechanisms influenced by cis-regulatory variants is essential to understand gene regulation and ultimately disease pathophysiology. Combining bioinformatics and public domain chromatin information with quantitative proteomics supports prediction of cis-regulatory variants and enabled identification of allele-dependent binding of both, transcription factors and coregulators at the type 2 diabetes associated PPARG locus. We found rs7647481A nonrisk allele binding of Yin Yang 1 (YY1), confirmed by allele-specific chromatin immunoprecipitation in primary adipocytes. Quantitative proteomics also found the coregulator RING1 and YY1 binding protein (RYBP) whose mRNA levels correlate with improved insulin sensitivity in primary adipose cells carrying the rs7647481A nonrisk allele. Our findings support a concept with diverse cis-regulatory variants contributing to disease pathophysiology at one locus. Proteome-wide identification of both, transcription factors and coregulators, can profoundly improve understanding of mechanisms underlying genetic associations.en
dc.language.isoen_USen
dc.publisherOxford University Pressen
dc.relation.isversionofdoi:10.1093/nar/gkx105en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389726/pdf/en
dash.licenseLAAen_US
dc.titleAllele-specific quantitative proteomics unravels molecular mechanisms modulated by cis-regulatory PPARG locus variationen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalNucleic Acids Researchen
dash.depositing.authorClaussnitzer, Melinaen_US
dc.date.available2017-05-01T19:27:40Z
dc.identifier.doi10.1093/nar/gkx105*
dash.authorsorderedfalse
dash.contributor.affiliatedClaussnitzer, Melina


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