Principal Investigator – MPI for Biology of Ageing
Chromatin is the complex of DNA and proteins that can be found in the nucleus of a cell. The basic unit of chromatin is the nucleosome that consists of DNA wrapped around an octamer of highly conserved histone proteins. The nucleosomes help to compact the DNA, but also serve as a gatekeeper for access to the genetic material. Over the last two decades, research revealed that the regulation of chromatin is at the heart of every DNA-dependent process, like transcription, replication and repair. This regulation, which is mediated by posttranslational modifications, is often referred to as epigenetics. Misregulation of epigenetic control has been implicated in many diseases, most notably cancer. However, only very recently it has become apparent that chromatin is undergoing dramatic changes during ageing.
Our research: Dr. Tessarz and his team use two different model systems to address the question of how histones modulate transcriptional processes and how chromatin changes with age. Using budding yeast as a model, they address mechanistic consequences of chromatin alterations on transcriptional processes and lifespan. Embryonic and adult stem cells serve as a model to investigate the interplay of environment, metabolism on epigenetics and ageing. To do this they employ a variety of different methodologies, including biochemistry, genetics and genomics.
Our successes: We have recently identified a novel histone modification that is localized exclusively at the rDNA region of the genome (a region well-known to be responsible to contribute to ageing at least in the yeast S. cerevisiae), making it the first histone modification dedicated to one single polymerase.
Our goals: Our work will aim to answer questions like: What are the basic principles of chromatin alterations during ageing? How does the architecture and modifications of chromatin change? Can these changes be reversed? If yes – would this benefit fitness during ageing?
Our methods/techniques: On the one hand we use S. cerevisiae as a model system to understand mechanistic consequences of epigenetic alterations and on the other hand, embryonic and primary adult stem cells to address the interplay between metabolism, epigenetics and differentiation processes. To do this, we rely on a variety of next-generation sequencing technologies, including ChIP- and RNA-Seq.
Figure 1: Genomic localisation of one histone modification (H2AQ105 methylation) in yeast. Depicted is one chromosome (XII). The upper track (blue/orange) shows the enrichment of the modification over the core histone. The orange peaks are sites of enrichment and show that this modification is specifically enriched over one particular region in the genome – rDNA locus that encodes for the ribosomal RNA genes.