Probe the function of histone lysine 36 methylation using histone H3 lysine 36 to methionine mutant transgene in mammalian cells

Dong Fang, Haiyun Gan, Heping Wang, Hui Zhou, Zhiguo Zhang

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Chondroblastoma is a cartilaginous tumor that typically arises under 25 y of age (80%). Recent studies have identified a somatic and heterozygous mutation at the H3F3B gene in over 90% chondroblastoma cases, leading to a lysine 36 to methionine replacement (H3.3K36M). In human cells, H3F3B gene is one of 2 genes that encode identical H3.3 proteins. It is not known how H3.3K36M mutant proteins promote tumorigenesis. We and others have shown that, the levels of H3K36 di- and tri-methylation (H3K36me2/me3) are reduced dramatically in chondroblastomas and chondrocytes bearing the H3.3K36M mutation. Mechanistically, H3.3K36M mutant proteins inhibit enzymatic activity of some, but not all H3K36 methyltransferases. Chondrocytes harboring the same H3F3B mutation exhibited the cancer cell associated phenotypes. Here, we discuss the potential effects of H3.3K36M mutation on epigenomes including H3K36 and H3K27 methylation and cellular phenotypes. We suggest that H3.3K36M mutant proteins alter epigenomes of specific progenitor cells, which in turn lead to cellular transformation and tumorigenesis.

Original languageEnglish (US)
Pages (from-to)1781-1789
Number of pages9
JournalCell Cycle
Volume16
Issue number19
DOIs
StatePublished - Oct 2 2017

Keywords

  • Asf1
  • Cancer cells
  • Chondroblastoma
  • Chromosomes
  • Epigenetic
  • H3K36me3
  • Histone methylation
  • Tumorigenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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