KDM2A/B lysine demethylases and their alternative isoforms in development and disease

Nucleus. 2018;9(1):431-441. doi: 10.1080/19491034.2018.1498707.

Abstract

Aberrant levels of histone modifications lead to chromatin malfunctioning and consequently to various developmental defects and human diseases. Therefore, the proteins bearing the ability to modify histones have been extensively studied and the molecular mechanisms of their action are now fairly well understood. However, little attention has been paid to naturally occurring alternative isoforms of chromatin modifying proteins and to their biological roles. In this review, we focus on mammalian KDM2A and KDM2B, the only two lysine demethylases whose genes have been described to produce also an alternative isoform lacking the N-terminal demethylase domain. These short KDM2A/B-SF isoforms arise through alternative promoter usage and seem to play important roles in development and disease. We hypothesise about the biological significance of these alternative isoforms, which might represent a more common evolutionarily conserved regulatory mechanism.

Keywords: KDM2A; KDM2B; lysine demethylase; epigenetics; chromatin; alternative isoform; alternative promoter.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Isoenzymes / deficiency
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Jumonji Domain-Containing Histone Demethylases / deficiency
  • Jumonji Domain-Containing Histone Demethylases / genetics
  • Jumonji Domain-Containing Histone Demethylases / metabolism*
  • Neoplasms / enzymology*
  • Neoplasms / metabolism

Substances

  • Isoenzymes
  • Jumonji Domain-Containing Histone Demethylases

Grants and funding

Our work is supported by the GACR grant P302/12/G157 from the Czech Science Foundation, and by the PROGRES Q28 grant from the Charles University in Prague.