Epigenetic regulation of pyruvate carboxylase gene expression in the postpartum liver

Walker, C. G., Crookenden, M. A., Henty, K. M., Handley, R. R., Kuhn-Sherlock, B., White, H. M., Donkin, S. S., Snell, R. G., Meier, S., Heiser, A., Loor, J. J., Mitchell, M. D. and Roche, J. R. (2016) Epigenetic regulation of pyruvate carboxylase gene expression in the postpartum liver. Journal of Dairy Science, 99 7: 5820-5827. doi:10.3168/jds.2015-10331


Author Walker, C. G.
Crookenden, M. A.
Henty, K. M.
Handley, R. R.
Kuhn-Sherlock, B.
White, H. M.
Donkin, S. S.
Snell, R. G.
Meier, S.
Heiser, A.
Loor, J. J.
Mitchell, M. D.
Roche, J. R.
Title Epigenetic regulation of pyruvate carboxylase gene expression in the postpartum liver
Journal name Journal of Dairy Science   Check publisher's open access policy
ISSN 1525-3198
0022-0302
Publication date 2016-07
Year available 2016
Sub-type Article (original research)
DOI 10.3168/jds.2015-10331
Open Access Status Not Open Access
Volume 99
Issue 7
Start page 5820
End page 5827
Total pages 8
Place of publication New York, NY, United States
Publisher Elsevier
Collection year 2017
Language eng
Formatted abstract
Hepatic gluconeogenesis is essential for maintenance of whole body glucose homeostasis and glucose supply for mammary lactose synthesis in the dairy cow. Upregulation of the gluconeogenic enzyme pyruvate carboxylase (PC) during the transition period is vital in the adaptation to the greater glucose demands associated with peripartum lactogenesis. The objective of this study was to determine if PC transcription in hepatocytes is regulated by DNA methylation and if treatment with a nonsteroidal anti-inflammatory drug (NSAID) alters methylation of an upstream DNA sequence defined as promoter 1. Dairy cows were left untreated (n = 20), or treated with a NSAID during the first 5 d postcalving (n = 20). Liver was biopsied at d 7 precalving and d 7, 14, and 28 postcalving. Total PC and transcript specific gene expression was quantified using quantitative PCR and DNA methylation of promoter 1 was quantified using bisulfite Sanger sequencing. Expression of PC changed over the transition period, with increased expression postcalving occurring concurrently with increased circulating concentration of nonesterified fatty acids. The DNA methylation percentage was variable at all sites quantified and ranged from 21 to 54% across the 15 CpG dinucleotides within promoter 1. The DNA methylation at wk 1 postcalving, however, was not correlated with gene expression of promoter 1-regulated transcripts and we did not detect an effect of NSAID treatment on DNA methylation or PC gene expression. Our results do not support a role for DNA methylation in regulating promoter 1-driven gene expression of PC at wk 1 postcalving. Further research is required to determine the mechanisms regulating increased PC expression over the transition period.
Keyword Epigenetic
Gluconeogenesis
Transcription
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
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