Related Experiment Video

Updated: Sep 20, 2025

A Protocol for Rapid Post-mortem Cell Culture of Diffuse Intrinsic Pontine Glioma DIPG
08:46

A Protocol for Rapid Post-mortem Cell Culture of Diffuse Intrinsic Pontine Glioma DIPG

Published on: March 7, 2017

17.1K

A specific form of cPRC1 containing CBX4 is co-opted to mediate oncogenic gene repression in diffuse midline glioma

Eimear Lagan1, Dáire Gannon2, Ademar Jesus Silva2

  • 1Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland; Cancer Research UK Edinburgh Centre, Institute of Genetics and Cancer University of Edinburgh, Edinburgh, UK; MRC Human Genetics Unit, Institute of Genetics and Cancer, The University of Edinburgh, Edinburgh, UK.

Molecular Cell
|May 22, 2025
PubMed

Insights

Researchers identified a specific PRC1 complex (CBX4/PCGF4) crucial for diffuse midline glioma (DMG) growth. This complex drives oncogenic gene repression, offering new therapeutic targets for this fatal childhood brain cancer.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Cancer Research

Background:

  • Diffuse midline glioma (DMG) is a deadly pediatric brain tumor linked to mutant histone H3 (H3K27M).
  • H3K27M mutation disrupts Polycomb repressive complex 2 (PRC2)-mediated H3K27 trimethylation (H3K27me3), yet PRC2 remains vital for DMG cells.
  • The precise molecular mechanisms driving DMG oncogenesis downstream of H3K27me3 are not fully understood.

Purpose of the Study:

  • To investigate the downstream molecular mechanisms of H3K27me3 alterations in DMG.
  • To identify specific protein complexes involved in oncogenic gene repression in DMG.
  • To explore potential therapeutic strategies targeting these mechanisms.

Main Methods:

  • Utilized functional assays to identify PRC1 complexes associated with H3K27me3.
  • Investigated the role of CBX4 and PCGF4 in DMG cell proliferation.
  • Analyzed the distribution of cPRC1 complexes in relation to H3K27me3 marks in DMG cells.

Main Results:

  • Discovered a novel canonical PRC1 (cPRC1) complex containing CBX4 and PCGF4 that mediates oncogenic gene repression in DMG.
  • CBX4/PCGF4-cPRC1 preferentially accumulates at H3K27me3-enriched CpG islands in DMG cells.
  • This specific cPRC1 complex, despite its low abundance, is essential for DMG cell growth.

Conclusions:

  • The study links altered H3K27me3 landscapes in DMG to imbalanced cPRC1 function.
  • CBX4/PCGF4-cPRC1 drives oncogenic gene repression, contributing to DMG pathogenesis.
  • These findings highlight CBX4/PCGF4-cPRC1 as a potential therapeutic target for diffuse midline glioma.
Keywords:
CBX4EZH2H3K27MH3K27me3PCGF4PRC1PRC2Polycombdiffuse intrinic pontine gliomadiffuse midline glioma

More Related Videos

Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis07:26

Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis

Published on: January 31, 2025

693
Modeling Astrocytoma Pathogenesis In Vitro and In Vivo Using Cortical Astrocytes or Neural Stem Cells from Conditional, Genetically Engineered Mice10:13

Modeling Astrocytoma Pathogenesis In Vitro and In Vivo Using Cortical Astrocytes or Neural Stem Cells from Conditional, Genetically Engineered Mice

Published on: August 12, 2014

13.5K

Related Concept Videos

The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.2K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
6.5K
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
4.4K
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
4.3K