The Hira complex regulates Gli3R-dependent transcription in Hedgehog signaling and medulloblastoma cell growth and migration. 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. Overall design: CUT&RUN experiment in NIH/3T3 mouse cell line with doxocycline inducible (Dox) expression of HA-Gli3R and Hira protein loss-of-function

刺猬信号通路（Hedgehog pathway）的活性调控，可由其主要效应因子——Gli转录因子（Gli transcription factors）的共激活因子与共抑制因子介导。尽管其激活过程已得到充分研究，但通路的抑制机制仍不甚明晰。
本研究鉴定出染色质重塑复合物Hira可与Gli3R蛋白相互作用，证实其功能缺失会改变Hh通路的活性，并对该观测效应背后的潜在机制进行了探究。
此外，本研究还明确Hira可影响Hh信号依赖性髓母细胞瘤Daoy细胞的存活能力与迁移能力。
本研究为深入解析Hh通路调控及Hh信号依赖性致癌过程提供了新的研究思路。
本研究得到了波兰国家科学中心（National Science Centre, NCN）PRELUDIUM项目（编号：2022/45/N/NZ3/02113）的资助。
实验整体设计：在NIH/3T3小鼠细胞系中开展CUT&RUN实验，该细胞系具备多西环素（Dox）诱导的HA-Gli3R表达系统，并设置Hira蛋白功能缺失组。