The histone H3.3K27M mutation in pediatric glioma reprograms H3K27 methylation and gene expression

Kui Ming Chan, Dong Fang, Haiyun Gan, Rintaro Hashizume, Chuanhe Yu, Mark Schroeder, Nalin Gupta, Sabine Mueller, C. David James, Robert Jenkins, Jann Sarkaria, Zhiguo Zhang*

*Corresponding author for this work

Research output: Contribution to journalArticle

320 Scopus citations

Abstract

Recent studies have identified a Lys 27-to-methionine (K27M) mutation at one allele of H3F3A, one of the two genes encoding histone H3 variant H3.3, in 60% of highgrade pediatric glioma cases. The median survival of this group of patients after diagnosis is ~1 yr. Here we show that the levels of H3K27 di- and trimethylation (H3K27me2 and H3K27me3) are reduced globally in H3.3K27M patient samples due to the expression of the H3.3K27M mutant allele. Remarkably, we also observed that H3K27me3 and Ezh2 (the catalytic subunit of H3K27 methyltransferase) at chromatin are dramatically increased locally at hundreds of gene loci in H3.3K27M patient cells. Moreover, the gain of H3K27me3 and Ezh2 at gene promoters alters the expression of genes that are associated with various cancer pathways. These results indicate that H3.3K27M mutation reprograms epigenetic landscape and gene expression, which may drive tumorigenesis.

Original languageEnglish (US)
Pages (from-to)985-990
Number of pages6
JournalGenes and Development
Volume27
Issue number9
DOIs
StatePublished - May 1 2013

    Fingerprint

Keywords

  • Gliomas
  • H3.3K27M
  • H3K27 methylation
  • PRC2
  • Pediatric

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Chan, K. M., Fang, D., Gan, H., Hashizume, R., Yu, C., Schroeder, M., Gupta, N., Mueller, S., David James, C., Jenkins, R., Sarkaria, J., & Zhang, Z. (2013). The histone H3.3K27M mutation in pediatric glioma reprograms H3K27 methylation and gene expression. Genes and Development, 27(9), 985-990. https://doi.org/10.1101/gad.217778.113