Histone H3K9 demethylase JMJD1A is a co-activator of erythropoietin expression under hypoxia

Int J Biochem Cell Biol. 2019 Apr:109:33-39. doi: 10.1016/j.biocel.2019.01.022. Epub 2019 Feb 1.

Abstract

Erythropoietin (EPO) is a secreted hormone that stimulates the production of red blood cells, and the level of EPO is increased under hypoxia. The expression of EPO is regulated not only by the hypoxia-inducible factor (HIF) but also partly through epigenetic modifications, including histone acetylation and methylation. In this study, we report that histone H3K9 demethylase JMJD1 A is regulated by HIF-2α in HepG2 cells under hypoxia. Knockdown or over-expression of JMJD1 A can decrease or increase EPO expression, respectively. JMJD1 A can interact with HIF-2α to form a co-activator complex, which binds to the hypoxia response elements of EPO and increases EPO expression by catalyzing demethylation of H3K9me2, a transcription suppression marker. The results demonstrate that JMJD1 A is a co-activator of EPO expression.

Keywords: Erythropoietin; HIF-2α; Histone demethylase; Hypoxia-inducible factor; JMJD1A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Biocatalysis
  • Erythropoietin / metabolism*
  • Gene Expression Regulation*
  • Hep G2 Cells
  • Histones / chemistry*
  • Histones / metabolism*
  • Humans
  • Hypoxia / enzymology
  • Hypoxia / genetics
  • Hypoxia / metabolism*
  • Jumonji Domain-Containing Histone Demethylases / genetics
  • Jumonji Domain-Containing Histone Demethylases / metabolism*
  • Lysine / metabolism
  • Male
  • Methylation
  • Mice
  • Mice, Inbred C57BL
  • Transcription, Genetic

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Histones
  • Erythropoietin
  • endothelial PAS domain-containing protein 1
  • Jumonji Domain-Containing Histone Demethylases
  • KDM3A protein, human
  • Kdm3a protein, mouse
  • Lysine