Chromatin remodeling activity of C-module-binding factor from Dictyostelium discoideum

• Applicant: Professor Dr. Thomas Winckler
• Subject Area: General Genetics and Functional Genome Biology
• Term: from 2010 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 183019701

Dynamic histone methylation plays an important role in the regulation of transcription, genome stability and epigenetic inheritance. It has been established in a multitude of publications over the last ten years that methylations of distinct lysine and arginine residues in the amino-terminal tails of histones H3 and H4 can be reversed by histone demethylases. Most of these enzymes possess Jumonji (JmjC) domains that are capable of removing methyl groups from histones by an oxidative demethylation reaction. Dictyostelids are ancient unicellular organisms that have a facultative multicellular phase in which the cells differentiate into several cell types and collaborate to build up fruiting bodies. Gene expression in the model dictyostelid, Dictyostelium discoideum, has been studied in much detail, but our knowledge on the contribution of chromatin remodeling to gene regulation in this organism is scarce. The genome of D. discoideum encodes 13 JmjC proteins that come into consideration as putative histone demethylases. We will express these JmjC proteins in a Dictyostelium-based expression system and investigate their catalytic activities based on in vitro demethylation assays using synthetic histone peptides. In addition, we will expand our previous work on the JmjC family transcription regulator CbfA and investigate in which multiprotein complexes CbfA acts to either activate or suppress the expression of its target genes in the D. discoideum genome.

• DFG Programme: Research Grants