Allele-specific quantitative proteomics unravels molecular mechanisms modulated by cis-regulatory PPARG locus variation

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Allele-specific quantitative proteomics unravels molecular mechanisms modulated by cis-regulatory PPARG locus variation

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Title: Allele-specific quantitative proteomics unravels molecular mechanisms modulated by cis-regulatory PPARG locus variation
Author: Lee, Heekyoung; Qian, Kun; von Toerne, Christine; Hoerburger, Lena; Claussnitzer, Melina; Hoffmann, Christoph; Glunk, Viktoria; Wahl, Simone; Breier, Michaela; Eck, Franziska; Jafari, Leili; Molnos, Sophie; Grallert, Harald; Dahlman, Ingrid; Arner, Peter; Brunner, Cornelia; Hauner, Hans; Hauck, Stefanie M.; Laumen, Helmut

Note: Order does not necessarily reflect citation order of authors.

Citation: Lee, 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.
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Abstract: Abstract 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.
Published Version: doi:10.1093/nar/gkx105
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389726/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:32630617
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