Chromatin; Epigenetic Repression; Signal Transduction
DNA, the carrier of genetic information in our cells, is organized with the help of histone proteins as chromatin. Histone modifications affect the chromatin structure and thereby important biological processes such as transcription, replication and DNA repair. Our group is specifically interested in the role of histone deacetylases (HDACs) in development and disease. HDAC1 gene disruption in mice leads to reduced proliferation and severe developmental problems resulting in embryonic lethality of HDAC1 knockout mice (Lagger et al., 2002). Surprisingly, absence or reduced expression of HDAC1 in murine or human teratomas led to increased proliferation and reduced differentiation and was linked with a more malignant phenotype (Lagger et al., 2010). By using conditional HDAC knockout mice we have recently revealed the function of HDAC1 and HDAC2 enzymes during epidermal development and tumorigenesis (Winter et al., 2013), in neurogenesis (Hagelkruys et al., 2014) and in collaboration with Wilfried Ellmeier during T cell development (Grausenburger et al, 2010; Boucheron et al.,2014). HDACs are inactivated by small molecule inhibitors that are currently tested in clinical trials fo treatment of cancer and neurological diseases. In ongoing projects we examine whether HDAC1 and HDAC2 are relevant targets for these drugs.
Techniques, methods & infrastructure
Mouse genetics, chromatin related methods, gene expression analysis