Keywords

Chromatin; Epigenetic Repression; Signal Transduction

Research group(s)

• Epigenetics

Research interests

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

Grants

• Mimicking isoform-specific HDAC inhibitors (2016)
  Source of Funding: FFG (Austrian Research Promotion Agency), BRIDGE early stage
  Principal Investigator
• Enzymatic and non-enzymatic functions of HDAC1 and HDAC2 (2015)
  Source of Funding: FWF (Austrian Science Fund), Stand-Alone Projects
  Principal Investigator
• HDAC1 and HDAC2 as regulators of tumorigenesis (2015)
  Source of Funding: FWF (Austrian Science Fund), Stand-Alone Projects
  Principal Investigator
• HDAC1 and HDAC2 as regulators of epidermal homeostasis (2013)
  Source of Funding: FWF (Austrian Science Fund), Stand-Alone Projects
  Principal Investigator

Selected publications

1. Sawicka, A. et al., 2014. H3S28 phosphorylation is a hallmark of the transcriptional response to cellular stress. Genome Res., 24(11), pp.1808-1820. Available at: http://dx.doi.org/10.1101/gr.176255.114.
2. Boucheron, N. et al., 2014. CD4+ T cell lineage integrity is controlled by the histone deacetylases HDAC1 and HDAC2. Nat Immunol, 15(5), pp.439-448. Available at: http://dx.doi.org/10.1038/ni.2864.
3. Hagelkruys, A. et al., 2014. A single allele of Hdac2 but not Hdac1 is sufficient for normal mouse brain development in the absence of its paralog. Development, 141(3), pp.604-616. Available at: http://dx.doi.org/10.1242/dev.100487.
4. Winter, M. et al., 2013. Divergent roles of HDAC1 and HDAC2 in the regulation of epidermal development and tumorigenesis. The EMBO Journal, 32(24), pp.3176-3191. Available at: http://dx.doi.org/10.1038/emboj.2013.243.
5. Lagger, S. et al., 2010. Crucial function of histone deacetylase 1 for differentiation of teratomas in mice and humans. The EMBO Journal, 29(23), pp.3992-4007. Available at: http://dx.doi.org/10.1038/emboj.2010.264.