Role of CDYL in translating histone modification patterns for chromatin organization and regulation

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The template of all genomic processes in eukaryotic cells is chromatin. Post-translational modifications (PTM) of histone proteins – besides DNA, the major constituents of chromatin – are thought to be key in regulating chromatin structure and function. Mechanistic insights into the molecular working mechanisms of histone PTMs are essential for understanding the biochemistry of epi-genetics, that is regulatory pathways which govern the readout of the genome. Methylation of histone H3 at lysine 9 (H3K9me3) is considered one of the hallmarks of heterochromatin. In previous work, we have identified CDYL as a novel protein specifically recognizing this histone PTM. While CDYL has been shown to possess transcriptional repressive activity – likely mediated through a transient interaction with a repressor complex – nothing is known regarding the chromatin regulatory function of CDYL. Preliminary analysis shows CDYL as an H3K9me3 chromatin interacting protein in vivo and in vitro. Moreover, loss of CDYL affects developmental of Xenopus laevis embryos. In this project, we will analyze the chromatin distribution of CDYL in relation to the genome and in respect to histone PTMs – especially H3K9me3. We will identify and analyze CDYL associated proteins essential for CDYL chromatin regulation. Effects of CDYL complexes onto chromatin conformation and organization will be investigated using biochemical and biophysical methods. Lastly, the biological significance of CDYL-H3K9me3 interaction for chromatin regulation will be analyzed in the Xenopus laevis model system.