Chromatin remodeling is by the so called “histone-code” involving various covalent modification of the histones such as acetylation, phosphorylation and methylation has been subject to very many studies and their importance is now very well accepted. However, the transcriptional state can also be regulated by many chromatin-associated protein complexes that are either involved in enhancing or fine-tuning of the promoter activity and, of course some of these respond to the altered contexts that arise from the histone, and DNA modifications. In this project we will focus on novel aspects of the histone methylation status and related “off-target” activities of the enzymes involved and their consequences in cellular physiology.
Epigenetic modifying enzymes play an important role in regulating breast cancer metastasis through non-histone targets.
To discover novel targets of the epigenetic modifiers in by integrating proteomic and high throughput sequencing techniques.
- Cellular models and treatments.
- Characterisation of the KMT and the KDM change.
- Promoter methylation analysis.
- Protein complex purification and proteomics.
- Immunoprecipitation assays.
- Characterisation of putative methylation target proteins.
- Lee et. al., EZH2-Generates a Methyl Degron that is Recognized by the DCAF1/DDB1/ CUL4 E3 Ubiquitin Ligase Complex. Molecular Cell, 48, 572–586, 2012.
- Lee et. al., Negative Regulation of Hypoxia Response by Induced Reptin Methylation. Molecular Cell. 39, 71-85, 2010.