We are working to understanding the influence of histone PTM binding proteins on nucleosome and chromatin dynamics. A majority of histone PTMs are located on disordered ends of histone proteins (tails). PTMs in this region appear to largely function as binding sites for chromatin regulatory proteins. It is clear that histone PTMs recruit complexes that introduce additional PTMs, remove PTMs and remodel nucleosomes. However, the direct impact of PTM binding proteins on nucleosome and chromatin dynamics is largely unknown. We have and continue to investigate two proteins that bind trimethylated histone H3 at lysine 36, LEDGF and Phf1 (Fig. 1).
Fig. 1 The structure of the tudor domain of Phf1 docked onto the nucleosome.
We find that both proteins directly influence DNA unwrapping and accessibility. This led to publications in Nucleic Acids Research and Nature Communications. We are further characterizing the impact of these PTM binding proteins and setting up single molecule experiments to investigate their influence on the kinetics of TF binding and dissociation.