The Hira complex regulates Gli3R-dependent transcription in Hedgehog signaling and medulloblastoma cell growth and migration

Regulation of the Hedgehog pathway activity may be supported by coactivators and corepresors of its main effectors- Gli transcription factors. While activation processes are well studied, repression mechanisms remain elusive. We identified chromatin remodelling complex Hira to interact with Gli3R protein, showed that its loss-of-function changes Hh pathway activity, and examined possible mechanism behind the observed effect. We also established that Hira influences the viability and migratory abilities of Hh-dependent medulloblastoma Daoy cells. Our study paves the way for a better understanding of processes involved in Hh pathway regulation and Hh-dependent carcinogenesis. This work was supported by grant from the National Science Centre (NCN): PRELUDIUM 2022/45/N/NZ3/02113. CUT&RUN experiment in NIH/3T3 mouse cell line with doxocycline inducible (Dox) expression of HA-Gli3R and Hira protein loss-of-function