作者
Ryo Shiraishi,Gabriele Cancila,Kohei Kumegawa,Jacob Torrejón,Irene Basili,Flavia Bernardi,Patricia Benites Goncalves da Silva,Wan-Chen Wang,Owen Chapman,Liying Yang,Maki Jami,Koji Nishitani,Yasuko Arai,Z. Xiao,Hua Yu,Vincenzina Lo Re,Véronique Marsaud,Julie Talbot,Bérangère Lombard,Damarys Loew,Maho Jingu,Konstantin Okonechnikov,Masaki Sone,Norio Matsuki,Yoshitsugu Aoki,Stefan M. Pfister,Lukas Chávez,Mikio Hoshino,Reo Maruyama,Olivier Ayrault,Daisuke Kawauchi
摘要
Normal cells coordinate proliferation and differentiation by precise tuning of gene expression based on the dynamic shifts of the epigenome throughout the developmental timeline. Although non-mutational epigenetic reprogramming is an emerging hallmark of cancer, the epigenomic shifts that occur during the transition from normal to malignant cells remain elusive. Here, we capture the epigenomic changes that occur during tumorigenesis in a prototypic embryonal brain tumor, medulloblastoma. By comparing the epigenomes of the different stages of transforming cells in mice, we identify nuclear factor I family of transcription factors, known to be cell fate determinants in development, as oncogenic regulators in the epigenomes of precancerous and cancerous cells. Furthermore, genetic and pharmacological inhibition of NFIB validated a crucial role of this transcription factor by disrupting the cancer epigenome in medulloblastoma. Thus, this study exemplifies how epigenomic changes contribute to tumorigenesis via non-mutational mechanisms involving developmental transcription factors.