Genetic control of differential acetylation in diabetic rats
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 t...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Public Library of Science
2014
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| _version_ | 1826277400714936320 |
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| author | Kaisaki, P Otto, G McGouran, J Toubal, A Argoud, K Waller-Evans, H Finlay, C Caldérari, S Bihoreau, M Kessler, B Gauguier, D Mott, R |
| author_facet | Kaisaki, P Otto, G McGouran, J Toubal, A Argoud, K Waller-Evans, H Finlay, C Caldérari, S Bihoreau, M Kessler, B Gauguier, D Mott, R |
| author_sort | Kaisaki, P |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T23:28:20Z |
| format | Journal article |
| id | oxford-uuid:6b2e976d-0c52-4968-86b1-cd90ec2b44da |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:28:20Z |
| publishDate | 2014 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:6b2e976d-0c52-4968-86b1-cd90ec2b44da2022-03-26T19:02:04ZGenetic control of differential acetylation in diabetic ratsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6b2e976d-0c52-4968-86b1-cd90ec2b44daEnglishSymplectic Elements at OxfordPublic Library of Science2014Kaisaki, POtto, GMcGouran, JToubal, AArgoud, KWaller-Evans, HFinlay, CCaldérari, SBihoreau, MKessler, BGauguier, DMott, RPost-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. |
| spellingShingle | Kaisaki, P Otto, G McGouran, J Toubal, A Argoud, K Waller-Evans, H Finlay, C Caldérari, S Bihoreau, M Kessler, B Gauguier, D Mott, R Genetic control of differential acetylation in diabetic rats |
| title | Genetic control of differential acetylation in diabetic rats |
| title_full | Genetic control of differential acetylation in diabetic rats |
| title_fullStr | Genetic control of differential acetylation in diabetic rats |
| title_full_unstemmed | Genetic control of differential acetylation in diabetic rats |
| title_short | Genetic control of differential acetylation in diabetic rats |
| title_sort | genetic control of differential acetylation in diabetic rats |
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