JMJD3 as an epigenetic regulator in development and disease

Int J Biochem Cell Biol. 2015 Oct;67:148-57. doi: 10.1016/j.biocel.2015.07.006. Epub 2015 Jul 17.

Abstract

Gene expression is epigenetically regulated through DNA methylation and covalent chromatin modifications, such as acetylation, phosphorylation, ubiquitination, sumoylation, and methylation of histones. Histone methylation state is dynamically regulated by different groups of histone methyltransferases and demethylases. The trimethylation of histone 3 (H3K4) at lysine 4 is usually associated with the activation of gene expression, whereas trimethylation of histone 3 at lysine 27 (H3K27) is associated with the repression of gene expression. The polycomb repressive complex contains the H3K27 methyltransferase Ezh2 and controls dimethylation and trimethylation of H3K27 (H3K27me2/3). The Jumonji domain containing-3 (Jmjd3, KDM6B) and ubiquitously transcribed X-chromosome tetratricopeptide repeat protein (UTX, KDM6A) have been identified as H3K27 demethylases that catalyze the demethylation of H3K27me2/3. The role and mechanisms of both JMJD3 and UTX have been extensively studied for their involvement in development, cell plasticity, immune system, neurodegenerative disease, and cancer. In this review, we will focus on recent progresses made on understanding JMJD3 in the regulation of gene expression in development and diseases. This article is part of a Directed Issue entitled: Epigenetics dynamics in development and disease.

Keywords: H3K27; Histone demethylation; Jmjd3; Jumonji; Utx.

Publication types

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

MeSH terms

  • Animals
  • Chromatin / chemistry
  • Chromatin / metabolism
  • Enhancer of Zeste Homolog 2 Protein
  • Epigenesis, Genetic*
  • Gene Expression Regulation, Developmental
  • Germ Layers / cytology
  • Germ Layers / growth & development
  • Germ Layers / metabolism
  • Histone Demethylases / genetics*
  • Histone Demethylases / immunology
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • Immunity, Innate
  • Jumonji Domain-Containing Histone Demethylases / genetics*
  • Jumonji Domain-Containing Histone Demethylases / immunology
  • Lysine / metabolism
  • Mice
  • Neoplasms / genetics*
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Neurodegenerative Diseases / genetics*
  • Neurodegenerative Diseases / immunology
  • Neurodegenerative Diseases / pathology
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / immunology
  • Polycomb Repressive Complex 2 / genetics*
  • Polycomb Repressive Complex 2 / immunology

Substances

  • Chromatin
  • Histones
  • Nuclear Proteins
  • Histone Demethylases
  • Jumonji Domain-Containing Histone Demethylases
  • KDM6A protein, human
  • KDM6B protein, human
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Polycomb Repressive Complex 2
  • Lysine