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Genome-wide 5-hydroxymethylcytosine (5hmC) emerges at early stage of in vitro differentiation of a putative hepatocyte progenitor
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Genome-wide 5-hydroxymethylcytosine (5hmC) emerges at early stage of in vitro differentiation of a putative hepatocyte progenitor
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Journal Article
Genome-wide 5-hydroxymethylcytosine (5hmC) emerges at early stage of in vitro differentiation of a putative hepatocyte progenitor
2020
Overview
A basic question linked to differential patterns of gene expression is how cells reach different fates despite using the same DNA template. Since 5-hydroxymethylcytosine (5hmC) emerged as an intermediate metabolite in active DNA demethylation, there have been increasing efforts to elucidate its function as a stable modification of the genome, including a role in establishing such tissue-specific patterns of expression. Recently we described TET1-mediated enrichment of 5hmC on the promoter region of the master regulator of hepatocyte identity,
HNF4A
, which precedes differentiation of liver adult progenitor cells
in vitro
. Here, we studied the genome-wide distribution of 5hmC at early
in vitro
differentiation of human hepatocyte-like cells. We found a global increase in 5hmC as well as a drop in 5-methylcytosine after one week of
in vitro
differentiation from bipotent progenitors, at a time when the liver transcript program is already established. 5hmC was overall higher at the bodies of overexpressed genes. Furthermore, by modifying the metabolic environment, an adenosine derivative prevents 5hmC enrichment and impairs the acquisition of hepatic identity markers. These results suggest that 5hmC could be a marker of cell identity, as well as a useful biomarker in conditions associated with cell de-differentiation such as liver malignancies.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 38/77
/ 45/22
/ 45/61
/ 5-Methylcytosine - analogs & derivatives
/ 5-Methylcytosine - metabolism
/ Biochemistry, Molecular Biology
/ Cell Differentiation - genetics
/ DNA
/ Gene Expression Regulation, Developmental - genetics
/ Genomes
/ Hepatocyte Nuclear Factor 4 - genetics
/ Humanities and Social Sciences
/ Humans
/ Mixed Function Oxygenases - genetics
/ Promoter Regions, Genetic - genetics
/ Proto-Oncogene Proteins - genetics
/ Science
