TY  - JOUR
AU  - Shiraishi, Ryo
AU  - Cancila, Gabriele
AU  - Kumegawa, Kohei
AU  - Torrejon, Jacob
AU  - Basili, Irene
AU  - Bernardi, Flavia
AU  - Silva, Patricia Benites Goncalves da
AU  - Wang, Wanchen
AU  - Chapman, Owen
AU  - Yang, Liying
AU  - Jami, Maki
AU  - Nishitani, Kayo
AU  - Arai, Yukimi
AU  - Xiao, Zhize
AU  - Yu, Hua
AU  - Lo Re, Valentina
AU  - Marsaud, Véronique
AU  - Talbot, Julie
AU  - Lombard, Bérangère
AU  - Loew, Damarys
AU  - Jingu, Maho
AU  - Okonechnikov, Konstantin
AU  - Sone, Masaki
AU  - Motohashi, Norio
AU  - Aoki, Yoshitsugu
AU  - Pfister, Stefan M
AU  - Chavez, Lukas
AU  - Hoshino, Mikio
AU  - Maruyama, Reo
AU  - Ayrault, Olivier
AU  - Kawauchi, Daisuke
TI  - Cancer-specific epigenome identifies oncogenic hijacking by nuclear factor I family proteins for medulloblastoma progression.
JO  - Developmental cell
VL  - 59
IS  - 17
SN  - 1534-5807
CY  - New York, NY
PB  - Elsevier
M1  - DKFZ-2024-01209
SP  - 2302-2319.e12
PY  - 2024
N1  - 2024 Sep 9;59(17):2302-2319.e12
AB  - 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.
KW  - brain tumor (Other)
KW  - cerebellar granule cell (Other)
KW  - cerebellum (Other)
KW  - epigenome (Other)
KW  - medulloblastoma (Other)
KW  - mouse model (Other)
KW  - nuclear factor I (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:38834071
DO  - DOI:10.1016/j.devcel.2024.05.013
UR  - https://inrepo02.dkfz.de/record/290623
ER  -