Michael Rehli • Dept. Internal Medicine III • University Hospital • F.-J.-Strauss Allee 11 • 93053 Regensburg
DNA Methylation in Cancer
In mammals, methylation of cytosine residues in CpG dinucleotides is a frequent epigenetic mark that is required for normal embryonic development. DNA methylation plays important roles in gene regulation, e.g. in X chromosome inactivation, imprinting, or silencing of retrotransposons and is mostly associated with gene repression. Aberrant methylation patterns have been associated with diseases such as cancer, where the epigenetic silencing of tumor-suppressor genes often coincides with the aberrant methylation of CpG dinucleotides in so called CpG islands. Hypermethylation of CpG islands appears to be a tumor-type specific event and current research efforts concentrate on finding ways to exploit the diagnostic and therapeutic implications of epigenetic abnormalities. We developed tools that enable the generation of genome-wide profiles of DNA methylation in normal or cancer cells, and several lab members investigate the impact of CpG methylation on gene regulation and cancer development, in particular in acute myeloid leukemias and myelodysplastic syndromes.
Previous work from others as well as work from our lab suggests a major role for transcription factors in determining and maintaining DNA methylation profiles in health and disease. We are using both functional assays and global approaches, including high-throughput sequencing, mass spectrometry, and microarray technology, to define potential regulatory sequences in normal and neoplastic myeloid cells and to disect the relationship between DNA methylation changes and altered transcription factor binding at these regions.