KDM5B Is a Master Regulator of the H3K4-methylome in Stem Cells, Development and Cancer

Semin Cancer Biol. 2019 Aug;57:79-85. doi: 10.1016/j.semcancer.2018.11.001. Epub 2018 Nov 16.

Abstract

Epigenetic regulation of chromatin plays a critical role in controlling stem cell function and tumorigenesis. The histone lysine demethylase, KDM5B, which catalyzes the demethylation of histone 3 lysine 4 (H3K4), is important for embryonic stem (ES) cell differentiation, and is a critical regulator of the H3K4-methylome during early mouse embryonic pre-implantation stage development. KDM5B is also overexpressed, amplified, or mutated in many cancer types. In cancer cells, KDM5B regulates expression of oncogenes and tumor suppressors by modulating H3K4 methylation levels. In this review, we examine how KDM5B regulates gene expression and cellular fates of stem cells and cancer cells by temporally and spatially controlling H3K4 methylation levels.

Keywords: Cancer; Chromatin; Differentiation; Embryonic stem cells; Epigenetics; Gene expression; H3K4me3; Histone demethylase; KDM5B; Pluripotent.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biomarkers, Tumor
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / metabolism*
  • Epigenesis, Genetic*
  • Histones / metabolism*
  • Humans
  • Jumonji Domain-Containing Histone Demethylases / antagonists & inhibitors
  • Jumonji Domain-Containing Histone Demethylases / metabolism*
  • Methylation
  • Neoplasms / drug therapy
  • Neoplasms / etiology*
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Proteins / metabolism*
  • Repressor Proteins / antagonists & inhibitors
  • Repressor Proteins / metabolism*
  • Stem Cells / metabolism

Substances

  • Biomarkers, Tumor
  • Histones
  • Nuclear Proteins
  • Repressor Proteins
  • Jumonji Domain-Containing Histone Demethylases
  • KDM5B protein, human