Research – ACS Synthetic Biology – 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) ACS Synthetic Biol. (just accepted manuscript) https://pubs.acs.org/doi/pdf/10.1021/acssynbio.7b00281
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.
- Pre-print: Tandem Histone-Binding Domains Enhance the Activity of a Synthetic Chromatin Effector. bioRxiv. http://biorxiv.org/content/early/2017/06/03/145730
- Conference Proceeding: In Vitro Development of Synthetic Chromatin Proteins That Function in Live Cells. FASEB. http://www.fasebj.org/content/31/1_Supplement/922.8.short