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Current Projects

HDAC1/HDAC2 mutants with a single amino acid exchange in the catalytic center are still incorporated into co-regulator complexes and might mimic isoform-specific isoforms. They reduce the deacetylase activity of co-regulator complexes and thereby change the cellular gene expression program. We will study these mutants in murine skin tumor models and other disease models and will compare their effect with HDAC inhibitors.

Protein-protein interactions and post-translational modifications (PTMs) are crucial for the assembly and activation of HDAC1/HDAC2 multiprotein co-regulator complexes. We have generated a genetic toolbox consisting of constructs encoding a series of HDAC mutants affecting PTMs of HDAC1 and HDAC2. We will use these mutants to examine their effects on cellular homeostasis both in vitro in cell lines and in vivo in conditional knock-in mice.

Increased histone acetylation enhances lipogenesis and key lipogenic gene expression in sebocytes and adipocytes. We have generated a new murine model for conditional replacement of endogenous HDAC1 with a catalytically inactive HDAC1 mutant, specifically in keratinocytes and sebocytes. This model, together with a cultured human sebocytes cell line, will help to uncover the molecular mechanisms mediating the epigenetic control of cutaneous lipid metabolism by HDAC1.