Ontogeny, distribution and potential roles of 5-hydroxymethylcytosine in human liver function

Maxim Ivanov, Mart Kals, Marina Kacevska, Isabel Barragan, Kie Kasuga, Anders Rane, Andres Metspalu, Lili Milani, Magnus Ingelman-Sundberg

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)

Abstract

Background: Interindividual differences in liver functions such as protein synthesis, lipid and carbohydrate metabolism and drug metabolism are influenced by epigenetic factors. The role of the epigenetic machinery in such processes has, however, been barely investigated. 5-hydroxymethylcytosine (5hmC) is a recently re-discovered epigenetic DNA modification that plays an important role in the control of gene expression.Results: In this study, we investigate 5hmC occurrence and genomic distribution in 8 fetal and 7 adult human liver samples in relation to ontogeny and function. LC-MS analysis shows that in the adult liver samples 5hmC comprises up to 1% of the total cytosine content, whereas in all fetal livers it is below 0.125%. Immunohistostaining of liver sections with a polyclonal anti-5hmC antibody shows that 5hmC is detected in most of the hepatocytes. Genome-wide mapping of the distribution of 5hmC in human liver samples by next-generation sequencing shows significant differences between fetal and adult livers. In adult livers, 5hmC occupancy is overrepresented in genes involved in active catabolic and metabolic processes, whereas 5hmC elements which are found in genes exclusively in fetal livers and disappear in the adult state, are more specific to pathways for differentiation and development.Conclusions: Our findings suggest that 5-hydroxymethylcytosine plays an important role in the development and function of the human liver and might be an important determinant for development of liver diseases as well as of the interindividual differences in drug metabolism and toxicity.

Original languageEnglish
Article numberR83
JournalGenome biology
Volume14
Issue number8
DOIs
Publication statusPublished - 2013 Aug 19

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics
  • Cell Biology

Fingerprint Dive into the research topics of 'Ontogeny, distribution and potential roles of 5-hydroxymethylcytosine in human liver function'. Together they form a unique fingerprint.

Cite this