Final Report Summary - TRANSMETH (Identification of novel functions and regulators of DNA methylation in mammals) DNA methylation is a process by which a methyl (CH3) group is added to DNA. This occurs mostly on one of the four nucleotides of DNA, the cytosine. The conversion of cytosine bases to 5-methylcytosine is catalysed by DNA methyltransferases (DNMTs). This small chemical modification of cytosines is abundant in mammalian genomes and has important regulatory functions. It is used by cells to modulate the expression of genes and fix some genes in a stable “off” state, which is vital for a number of biological processes such as embryonic development, organogenesis and sexual reproduction. This chemical mark of DNA needs to be tightly controlled because errors in DNA methylation can promote cancer. The project “TransMETH” is dedicated to the study of DNA methylation in mammalian genomes. Using a combination of genome-wide sequencing, mouse genetics, bioinformatics and molecular approaches, we generated comprehensive maps of DNA methylation and studied the functions of DNA methylation in regulating gene expression and cellular identity in various cell populations of the mammalian embryo. Furthermore we discovered novel molecular pathways responsible for recruiting DNA methylation at specific genomic sites in mouse embryonic cells. Finally we optimized novel molecular tools for gene specific manipulation of DNA methylation in mammalian cells. The project helped to better understand how DNA methylation patterns are established in the genome and contribute to regulate cellular decisions in mammals, which has also implications for understanding the mechanisms and consequences of aberrant DNA methylation in cancer.
