Biomimetic Artificial Epigenetic Code for Targeted Acetylation of Histones

Junichi Taniguchi, Yihong Feng, Ganesh N. Pandian, Fumitaka Hashiya, Takuya Hidaka, Kaori Hashiya, Soyoung Park, Toshikazu Bando, Shinji Ito, and Hiroshi Sugiyama; . Am. Chem. Soc., Article ASAP DOI: 10.1021/jacs.8b01518 Publication Date (Web): May 24, 2018

Recently, Ansari’s group reported a conjugate called Syn-TEF by coupling a PIP with another bromodomain inhibitor(+)-JQ1, selective to the bromodomain and extraterminal(BET) protein family. 45 Syn-TEF1 targeting expanded GAA repeats in the frataxin (FXN) gene successfully recruited BET protein BRD4 (bromodomain 4) to the gene locus in Friedreich’s ataxia (FRDA) patient-derived cells, resulting intranscriptional elongation of FXN. However, Syn-TEF and Bi-PIP target different members of the BD protein family and, therefore, are demonstrated to cause different outcomes; i.e.,while Syn-TEF causes BRD4-dependent transcriptional elongation, Bi-PIP causes P300 dependent histone acetylation. Thus,Bi-PIP and Syn-TEF can be used for different purposes, and this allows us to expand the range of potential applications of the synthetic epigenetic regulators.

 Biomimetic Artificial Epigenetic Code for Targeted Acetylation of Histones