Our joint publication with Dr. Jack Wong's epigenetics lab has been accepted by GUT. NRF2 is known to be a transcription factor and the major regulator that helps cells to overcome oxidative stress by initiating transcription of a repertoire of antioxidant genes. How NRF2 activates this adaptive response in an expeditious manner to ensure liver cancer cells survive high oxidative stress?
In this work, we identified a histone chaperone, the FACT complex, is responsible for NRF2-mediated transcription elongation of antioxidant genes. NRF2 initiates transcription when liver cancer cells encounter oxidative stress. The FACT complex is stabilized by oxidative stress and is further induced by NRF2. With the FACT complex, nucleosome could be reassembled and disassembled quickly to allow RNA polymerase to pass through chromatin during elongation to accelerate antioxidant gene transcription. Excitingly, a FACT inhibitor, curaxin, is able to reverse the event and suppress liver cancer growth in our mouse model.
Congratulations to Jialing for her exciting finding being accepted for publication!
Histone chaperone FACT complex mediates oxidative stress response to promote liver cancer progression. Gut. 2019 Aug 22. pii: gutjnl-2019-318668. doi: 10.1136/gutjnl-2019-318668. [Epub ahead of print]