Transcriptional and epigenetic networks and function of histone deacetylases in mammalsMolecular mechanism underlying plasticity
Stem cells give rise to differentiated cells through gradual establishment of lineage-specific gene expression programs. These result from a complex interplay of signal transduction cascades, genetic hierarchies of transcription factors and epigenetic chromatin modifiers. This creates a molecular code unique to each cell type that defines its properties and fate.
We are interested in the molecular mechanisms underlying cellular plasticity and cell-specific gene expression in a genetically tractable system and concentrate on the transcriptional and epigenetic control of lymphoid (B) cell development. For this, we study several transcription factors and epigenetic regulators that may be relevant for B cell development.
Focus on HDACs
In addition, we have a central focus on histone deacetylases (HDACs). Acetylation of histones represents a crucial epigenetic annotation of chromatin, which participates significantly in the regulation of gene expression. In addition, non-histone protein acetylation is involved in an expanding range of cellular processes. HDACs remove acetyl groups from histone N-terminal tails and thereby contribute to chromatin condensation and to the modulation of gene expression. Although the biological role of HDACs in mammals is still poorly understood, it is clear that these proteins are important in cancer as well as in various other diseases such as autoimmunity or neurodegeneration. HDACs therefore are valuable potential therapeutic targets in a number of pathological settings.
We use a broad range of methods, including the generation and analysis of transgenic or conditionally targeted mice as well as functional genomics and proteomics.
FMI report pages for Patrick Matthias