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Genetic control of differential acetylation in diabetic rats

Kaisaki, Pamela J., Otto, Georg W., McGouran, Joanna F., Toubal, Amine, Argoud, Karène, Waller-Evans, Helen, Finlay, Clare, Caldérari, Sophie, Bihoreau, Marie-Thérèse, Kessler, Benedikt M., Gauguier, Dominique and Mott, Richard 2014. Genetic control of differential acetylation in diabetic rats. PLoS ONE 9 (4) , e94555. 10.1371/journal.pone.0094555

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Abstract

Post-translational protein modifications such as acetylation have significant regulatory roles in metabolic processes, but their relationship to both variation in gene expression and DNA sequence is unclear. We address this question in the Goto-Kakizaki (GK) rat inbred strain, a model of polygenic type 2 diabetes. Expression of the NAD-dependent deacetylase Sirtuin-3 is down-regulated in GK rats compared to normoglycemic Brown Norway (BN) rats. We show first that a promoter SNP causes down-regulation of Sirtuin-3 expression in GK rats. We then use mass-spectrometry to identify proteome-wide differential lysine acetylation of putative Sirtuin-3 protein targets in livers of GK and BN rats. These include many proteins in pathways connected to diabetes and metabolic syndrome. We finally sequence GK and BN liver transcriptomes and find that mRNA expression of these targets does not differ significantly between GK and BN rats, in contrast to other components of the same pathways. We conclude that physiological differences between GK and BN rats are mediated by a combination of differential protein acetylation and gene transcription and that genetic variation can modulate acetylation independently of expression.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Biosciences
Subjects: Q Science > QH Natural history > QH426 Genetics
Q Science > QR Microbiology
Additional Information: © 2014 Kaisaki et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Publisher: Public Library of Science
ISSN: 1932-6203
Date of First Compliant Deposit: 30 March 2016
Date of Acceptance: 18 March 2014
Last Modified: 20 Feb 2019 15:32
URI: http://orca-mwe.cf.ac.uk/id/eprint/66953

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