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Epigenetic and SP1-mediated regulation is involved in the repression of galactokinase 1 gene in the liver of neonatal piglets born to betaine-supplemented sows
Nanjing Agr Univ, Key Lab Anim Physiol & Biochem, Nanjing 210095, Jiangsu, Peoples R China..
Nanjing Agr Univ, Key Lab Anim Physiol & Biochem, Nanjing 210095, Jiangsu, Peoples R China..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Nanjing Agr Univ, Key Lab Anim Physiol & Biochem, Nanjing 210095, Jiangsu, Peoples R China..
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2017 (English)In: European Journal of Nutrition, ISSN 1436-6207, E-ISSN 1436-6215, Vol. 56, no 5, 1899-1909 p.Article in journal (Refereed) Published
Abstract [en]

Purpose: In this study, we sought to investigate the effects of maternal betaine supplementation on the expression and regulation of GALK1 gene in the liver of neonatal piglets.

Methods: Sixteen sows of two groups were fed control or betaine-supplemented diets (3 g/kg), respectively, throughout the pregnancy. Newborn piglets were individually weighed immediately after birth, and one male piglet close to mean body weight from the same litter was selected and killed before suckling. Serum samples of newborn piglets were analyzed for biochemical indexes, hormone and amino acid levels. Liver samples were analyzed for GALK1 expression by real-time PCR and western blotting, while GALK1 regulational mechanism was analyzed by methylated DNA immunoprecipitation, chromatin immunoprecipitation and microRNAs expression.

Results: Betaine-exposed neonatal piglets had lower serum concentration of galactose, which was associated with significantly down-regulated hepatic GALK1 expression. The repression of GALK1 mRNA expression was associated with DNA hypermethylation and more enriched repression histone mark H3K27me3 on its promoter. Binding sites of SP1, GR and STAT3 were predicted on GALK1 promoter, and decreased SP1 protein content and lower SP1 binding to GALK1 promoter were detected in the liver of betaine-exposed piglets. Furthermore, the expression of miRNA-149 targeting GALK1 was up-regulated in the liver of betaine-exposed piglets, along with elevated miRNAs-processing enzymes Dicer and Ago2.

Conclusions: Our results suggest that maternal dietary betaine supplementation during gestation suppresses GALK1 expression in the liver of neonatal piglets, which involves complex gene regulation mechanisms including DNA methylation, histone modification, miRNAs expression and SP1-mediated transcriptional modulation.

Place, publisher, year, edition, pages
2017. Vol. 56, no 5, 1899-1909 p.
Keyword [en]
Galactokinase 1, Galactose, Betaine, Piglets, Methylation, miRNA-149
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-333071DOI: 10.1007/s00394-016-1232-yISI: 000406523700008PubMedID: 27250629OAI: oai:DiVA.org:uu-333071DiVA: diva2:1155713
Note

Demin Cai, Mengjie Yuan and Haoyu Liu have contributed equally to this work.

Available from: 2017-11-09 Created: 2017-11-09 Last updated: 2017-11-09Bibliographically approved

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