2. Academic Validation
  3. Cancer-specific epigenome identifies oncogenic hijacking by nuclear factor I family proteins for medulloblastoma progression

Cancer-specific epigenome identifies oncogenic hijacking by nuclear factor I family proteins for medulloblastoma progression

  • Dev Cell. 2024 May 31:S1534-5807(24)00330-7. doi: 10.1016/j.devcel.2024.05.013.
Ryo Shiraishi 1,  Gabriele Cancila 2,  Kohei Kumegawa 3,  Jacob Torrejon 2,  Irene Basili 2,  Flavia Bernardi 2,  Patricia Benites Goncalves da Silva 4,  Wanchen Wang 1,  Owen Chapman 5,  Liying Yang 6,  Maki Jami 1,  Kayo Nishitani 1,  Yukimi Arai 1,  Zhize Xiao 1,  Hua Yu 2,  Valentina Lo Re 2,  Véronique Marsaud 2,  Julie Talbot 2,  Bérangère Lombard 7,  Damarys Loew 7,  Maho Jingu 8,  Konstantin Okonechnikov 4,  Masaki Sone 9,  Norio Motohashi 10,  Yoshitsugu Aoki 10,  Stefan M Pfister 4,  Lukas Chavez 5,  Mikio Hoshino 1,  Reo Maruyama 11,  Olivier Ayrault 12,  Daisuke Kawauchi 13
Affiliations

Affiliations

  • 1 Department of Biochemistry and Cellular Biology, National Center of Neurology and Psychiatry (NCNP), Tokyo 187-8502, Japan.
  • 2 Institut Curie, PSL Research University, CNRS UMR, INSERM, Université Paris Sud, Université Paris-Saclay, CNRS UMR 3347, INSERM U1021, Orsay 91400, France.
  • 3 Cancer Cell Diversity Project, NEXT-Ganken Program, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan.
  • 4 Hopp Children's Cancer Center Heidelberg (KiTZ), German Cancer Research Center (DKFZ) and Heidelberg University Hospital, Heidelberg 69120, Germany.
  • 5 Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
  • 6 Project for Cancer Epigenomics, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan.
  • 7 Institut Curie, PSL Research University, CurieCoreTech Mass Spectrometry Proteomics, Paris 75005, France.
  • 8 Department of Biochemistry and Cellular Biology, National Center of Neurology and Psychiatry (NCNP), Tokyo 187-8502, Japan; Department of Biomolecular Science, Graduate School of Science, Toho University, Chiba 274-8510, Japan.
  • 9 Department of Biomolecular Science, Graduate School of Science, Toho University, Chiba 274-8510, Japan.
  • 10 Department of Molecular Therapy, National Center of Neurology and Psychiatry (NCNP), Tokyo 187-8502, Japan.
  • 11 Cancer Cell Diversity Project, NEXT-Ganken Program, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan; Project for Cancer Epigenomics, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan. Electronic address: reo.maruyama@jfcr.or.jp.
  • 12 Institut Curie, PSL Research University, CNRS UMR, INSERM, Université Paris Sud, Université Paris-Saclay, CNRS UMR 3347, INSERM U1021, Orsay 91400, France. Electronic address: olivier.ayrault@curie.fr.
  • 13 Department of Biochemistry and Cellular Biology, National Center of Neurology and Psychiatry (NCNP), Tokyo 187-8502, Japan. Electronic address: kawauchi@med.nagoya-cu.ac.jp.
PMID: 38834071 DOI: 10.1016/j.devcel.2024.05.013
Abstract

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.

Keywords

brain tumor; cerebellar granule cell; cerebellum; epigenome; medulloblastoma; mouse model; nuclear factor I.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z