Functional epigenetics and chromatin regulation
Chromatin proteins such as histones are highly covalently modified. The complexity and diversity of histone modifications add largely to the capacity of the genome to store and process information. We are currently only beginning to understand the many implications of this epigenetic information for biology and disease. Interestingly, histone-modifying enzymes are rearranged, mutated or deleted in almost all types of cancers, and small molecule inhibitors are effective in clinical use, giving rise to the promising field of medical epigenetics.
Our focus is on medical epigenetics, with a long-term aim to apply mechanistic insights towards therapy, e.g. by identifying novel therapeutic targets or new diagnostic markers.. We are currently identifying and studying new histone modifications. We are deciphering how these modifications are inherited, how they regulate gene expression/chromatin dynamics, and in particular their role in disease processes such as cancer. Whilst it is still under discussion if histone modifications form a true "code", it has now been established that changes of histone modifications (and of their ”readers”) are involved in the regulation of all genes and as such can initiate disease processes. Therefore the significance of studying chromatin modifications extends far beyond the field of chromatin research and has clear medical relevance.
Importantly, the functional characterisation of new histone modifications will open up possibilities to develop new strategies in cancer diagnostics and prognosis. The identification of novel modifying enzymes will provide us with new targets for epigenetic therapy of diseases where epigenetic states have become distorted.
Our lab is part of the ‘Cellular signaling and nuclear dynamics’ programme”.
Our lab is member of the FP7 EpiGeneSys NoE (http://www.epigenesys.eu/) and the Medical Epigenetics Initiative.
If you are interested in joining the lab, please email directly to: email@example.com
Deciphering the functions of novel modifications represents a key challenge in biology. We are in particular interested in how histone modifications integrate in normal biological processes e.g. cell proliferation, development or epigenetic reprogramming and also their deregulation in diseases. Our unique approach will allow us to (i) establish the function of novel histone modifications as gatekeepers of the genome and their role in tumorigenesis, (ii) understand thoroughly epigenetic mechanisms associated with cancer and (iii) identify new tumor markers and novel therapeutical targets (by identifying novel enzymes and pathways) that can have an impact on disease outcome and prognosis.
The current main project areas of our group are:
1. To determine the role of linker histone H1 modifications and of H1 variants in the regulation of gene expression, chromatin dynamics, development and disease processes (Kamierniarz et al., 2012). We recently integrated for the first time H1 variants into epigenomic maps (Izzo et al., 2013) forming the foundation for further in vivo studies. This will enable us to revisit the role of H1 from a mere structural chromatin component towards more specific functions.
2. To identify and functionally characterise new sites and new types of histone modifications, with a focus on modifications in the core of the nucleosome. We recently demonstrated a causative function for modifications within the nucleosome in stimulating transcription, answering the big question in the field about causality of histone modifications (Tropberger et al., 2013; Tropberger and Schneider 2013; di Cerbo et al., 2014). Currently we are mapping additional modifications globally, identifying the modifying enzymes and analysing their role in transcription, chromatin dynamics, development and especially their deregulation in diseases. We are establishing a comprehensive model for the function of modifications in the core of the nucleosome in “normal” chromatin and in tumorigenesis.
3. The identification of novel players in chromatin organisation. We are studying the role of non-histone proteins (and RNA) in chromatin integrity, in establishing and maintaining the dynamic nature of chromatin, as well as in genome stability and integrity (Kappes et al., 2011).
4. To understand the inheritance of epigenetic states in single cells. We are studying the inheritance of epigenetics states in individual cells through multiple generations, with the aim to identify factors that mediate this inheritance and to establish predictive models of their inheritance. These single-cell experiments shed light on the consequence of epigenetic changes on transcription dynamics and can be exploited for understanding disease progression.
- Robert SCHNEIDER - Gutenberg prize - Cercle Gutenberg - 2011
- Robert SCHNEIDER - Member of Epigenesys Network of Excellence - Epigenesys Network of Excellence - 2011
- Robert SCHNEIDER - Member of BIOS Excellence Cluster - BIOS Excellence Cluster - 2008
- Robert SCHNEIDER - ERC Starting grant - European Research Council (ERC) - 2007
- Robert SCHNEIDER - Career Development Award (CDA) - Human Frontier Science Program (HFSP) - 2005
- Robert SCHNEIDER - Long-term fellowship - Human Frontier Science Program (HFSP) - 2001
- Robert SCHNEIDER - Long-term fellowship - European Molecular Biology Organization (EMBO) - 2000
- March 25, 2014 - Histones hit the mark
- Aug. 1, 2013 - Keep chromatin locked? Ask for the right combination!
- June 6, 2013 - Give me your genomic position, I will tell you who you are!
- Feb. 14, 2013 - A new element in the gene expression puzzle
- May 31, 2012 - A unified phylogeny-based nomenclature for histone variants
- April 15, 2012 - New roles of Histone H1 in transcription
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Trends Genet Jan 2016 ; 32:42-56 .
Epigenetics Aug. 2, 2016 ; 11:553-62 .
Biochim Biophys Acta Mar 2016 ; 1859:486-95 .