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

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 (5h...

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Autores principales: Ivanov, Maxim, Kals, Mart, Kacevska, Marina, Barragan, Isabel, Kasuga, Kie, Rane, Anders, Metspalu, Andres, Milani, Lili, Ingelman-Sundberg, Magnus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4054829/
https://www.ncbi.nlm.nih.gov/pubmed/23958281
http://dx.doi.org/10.1186/gb-2013-14-8-r83
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author Ivanov, Maxim
Kals, Mart
Kacevska, Marina
Barragan, Isabel
Kasuga, Kie
Rane, Anders
Metspalu, Andres
Milani, Lili
Ingelman-Sundberg, Magnus
author_facet Ivanov, Maxim
Kals, Mart
Kacevska, Marina
Barragan, Isabel
Kasuga, Kie
Rane, Anders
Metspalu, Andres
Milani, Lili
Ingelman-Sundberg, Magnus
author_sort Ivanov, Maxim
collection PubMed
description 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.
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spelling pubmed-40548292014-06-12 Ontogeny, distribution and potential roles of 5-hydroxymethylcytosine in human liver function Ivanov, Maxim Kals, Mart Kacevska, Marina Barragan, Isabel Kasuga, Kie Rane, Anders Metspalu, Andres Milani, Lili Ingelman-Sundberg, Magnus Genome Biol Research 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. BioMed Central 2013 2013-08-19 /pmc/articles/PMC4054829/ /pubmed/23958281 http://dx.doi.org/10.1186/gb-2013-14-8-r83 Text en Copyright © 2013 Ivanov et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Ivanov, Maxim
Kals, Mart
Kacevska, Marina
Barragan, Isabel
Kasuga, Kie
Rane, Anders
Metspalu, Andres
Milani, Lili
Ingelman-Sundberg, Magnus
Ontogeny, distribution and potential roles of 5-hydroxymethylcytosine in human liver function
title Ontogeny, distribution and potential roles of 5-hydroxymethylcytosine in human liver function
title_full Ontogeny, distribution and potential roles of 5-hydroxymethylcytosine in human liver function
title_fullStr Ontogeny, distribution and potential roles of 5-hydroxymethylcytosine in human liver function
title_full_unstemmed Ontogeny, distribution and potential roles of 5-hydroxymethylcytosine in human liver function
title_short Ontogeny, distribution and potential roles of 5-hydroxymethylcytosine in human liver function
title_sort ontogeny, distribution and potential roles of 5-hydroxymethylcytosine in human liver function
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4054829/
https://www.ncbi.nlm.nih.gov/pubmed/23958281
http://dx.doi.org/10.1186/gb-2013-14-8-r83
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