Ladurner Lab Profile

Research Focus: Chromatin plasticity

Chromatin packages our cellular DNA, protects it from damage and ensures access by the right machines, at the right time. The smallest unit of chromatin is the nucleosome, a tightly-knit and stable assembly of histones and DNA. Yet, chromatin is a dynamic and versatile ('plastic') substrate. We now know that it regulates gene expression and the inheritance of our genome. Our lab focuses on discovering novel mechanisms employed by this chromatin-encoded, 'epigenetic' process of cellular control.

We are using biochemical, cellular, genomic and structural approaches to identify new proteins and new mechanisms that regulate chromatin plasticity. We tackle our diverse projects using an inter-disciplinary approach. Fundamentally, they focus on the question of molecular recognition. How is heterochromatin made and maintained? What is the role of histone variants role in chromatin dynamics? Who recognizes specific post-translational modifications in chromatin? What is the role of the metabolites that are used and/or are produced by chromatin enzymes in the regulation of gene expression? What molecular events occur in transcriptional repression? What is the biological role of the novel interactions we describe?

We have recently achieved breakthroughs on two fronts. First, we have identified a novel function in vertebrate chromatin: the histone variant macroH2A is a receptor for cellular NAD metabolites. Second, we have identified the novel function of the highly conserved macro domain: this is the first module that recognizes poly-ADP-ribose, a polymer of interest to the chromatin field. In addition, we have initiated a series of novel projects in fission yeast S. pombe transcriptional gene silencing and the RNAi pathway.