Research – bioRxiv Pre-print – Tandem histone binding domains enhance the activity of a synthetic chromatin effector
Tandem histone-binding domains enhance the activity of a synthetic chromatin effector
Tekel SJ, Vargas DA, Song L, LaBaer J, Haynes KA. (2017) bioRxiv. http://biorxiv.org/content/early/2017/06/03/145730
Here, we report the behavior of a re-engineered PcTF, a gene-regulating fusion protein that is designed to activate genes that have been suppressed by chromatin condensation in cancer cells. We added an extra histone-binding domain to create Pc2TF and observed 2- to 4-fold enhancement of target binding and target gene activation. The new design was inspired by natural proteins that also have double-motifs that contribute to target affinity. The specific combination of motifs in Pc2TF does not exist in nature. By using design rules inferred from pre-existing motif patterns, we have improved the performance a novel synthetic chromatin effector. This improved activity advances PcTF towards clinical translation for anti-cancer therapy.