Department of Toxicogenomics

MeDIP seq Methylated DNA Immunoprecipitation Sequencing

DNA-methylation is an enzymatically (DNA methyltransferase (DNMT) enzymes) conversion of a cytosine residue into a 5-methylctosine (5mC), which use S-adenosyl methionine (SAM) as the methyl donor. It is a type of epigenetic modification resulting in gene silencing. In addition to DNA methylation, gene expression can be regulated by other processes, such as: RNA turnover, mRNA processing and transcription rate. The 5mC can be enzymatically (ten-eleven-translocation (TET) enzymes) converted into 5-hydroxymethylcytosine (5hmC). This 5mC to 5hmC conversion may facilitate passive DNA demethylation by excluding maintenance of DNA methylation during cell division by DNMT1, which recognizes 5hmC poorly, suggesting that the presence of 5hmC will stop the gene silencing effect of 5mC. Recently, it has been shown that not only nuclear DNA (nDNA), but also mitochondrial DNA (mtDNA) may be subjected to epigenetic modifications (e.g. methylation). These mtDNA epigenetic modifications can modulate nDNA and nDNA epigenetic modifications may affect mtDNA.

It has been shown that oxidative stress plays a role in the Cà5mC and 5mCà5hmC conversion by increasing the DNMT and TET enzymes in nDNA. This mechanism is probably also involved in mtDNA. Furthermore it has been shown that oxidative stress plays a role in liver-toxicity. Therefore, the aim of this PhD project is to investigate how changes in patterns of 5mC and 5hmC, in nDNA and mtDNA, caused by oxidative stress are involved in the mechanisms of liver-toxicity. Our research questions are:

1. Does an oxidative stressor make normal liver cells more prone to (liver-)toxicity through hypo-methylation and-or hyper-hydroxymethylation? and,

2. Suppose that the mtDNA methylation levels change, what is than the effect on gene expression and DNA methylation in the nucleus and mitochondria?

Associated Staff

Prof T de Kok PhD

Prof. Theo de Kok graduated in 1988 as biologist at the Catholic University of Nijmegen, The Netherlands, with Microbiology and Toxicology as maj more ...

F Caiment PhD
Assistant Professor

Dr. Florian Caiment was born on the 15th of August 1980 in Troyes, France. After studying general biology in Reims then Nancy universities (Franc more ...

J Wolters MSc
PhD Student

Jarno Wolters was born on October 23rd 1989 in Heerlen. In 2009 he started his Bachelor ‘Biomedical Science’ at Maastricht University from which he gr more ...

Ing SMH Claessen
former staff

Ing Sandra Claessen was born in Herten on the 5th of August 1973. In 1997 she graduated from the technical school for medical biotechnology in Utrecht more ...