The Rheumatoid Arthritis Risk Variant CCR6DNP Regulates CCR6 via PARP-1

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The Rheumatoid Arthritis Risk Variant CCR6DNP Regulates CCR6 via PARP-1

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Title: The Rheumatoid Arthritis Risk Variant CCR6DNP Regulates CCR6 via PARP-1
Author: Li, Gang; Cunin, Pierre; Wu, Di; Diogo, Dorothée; Yang, Yu; Okada, Yukinori; Plenge, Robert M.; Nigrovic, Peter A.

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Citation: Li, Gang, Pierre Cunin, Di Wu, Dorothée Diogo, Yu Yang, Yukinori Okada, Robert M. Plenge, and Peter A. Nigrovic. 2016. “The Rheumatoid Arthritis Risk Variant CCR6DNP Regulates CCR6 via PARP-1.” PLoS Genetics 12 (9): e1006292. doi:10.1371/journal.pgen.1006292. http://dx.doi.org/10.1371/journal.pgen.1006292.
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Abstract: Understanding the implications of genome-wide association studies (GWAS) for disease biology requires both identification of causal variants and definition of how these variants alter gene function. The non-coding triallelic dinucleotide polymorphism CCR6DNP is associated with risk for rheumatoid arthritis, and is considered likely causal because allelic variation correlates with expression of the chemokine receptor CCR6. Using transcription activator-like effector nuclease (TALEN) gene editing, we confirmed that CCR6DNP regulates CCR6. To identify the associated transcription factor, we applied a novel assay, Flanking Restriction Enhanced Pulldown (FREP), to identify specific association of poly (ADP-ribose) polymerase 1 (PARP-1) with CCR6DNP consistent with the established allelic risk hierarchy. Correspondingly, manipulation of PARP-1 expression or activity impaired CCR6 expression in several lineages. These findings show that CCR6DNP is a causal variant through which PARP-1 regulates CCR6, and introduce a highly efficient approach to interrogate non-coding genetic polymorphisms associated with human disease.
Published Version: doi:10.1371/journal.pgen.1006292
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5023119/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:29407559
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