JMJD1C is required for the survival of acute myeloid leukemia by functioning as a coactivator for key transcription factors

Genes Dev. 2015 Oct 15;29(20):2123-39. doi: 10.1101/gad.267278.115.


RUNX1-RUNX1T1 (formerly AML1-ETO), a transcription factor generated by the t(8;21) translocation in acute myeloid leukemia (AML), dictates a leukemic program by increasing self-renewal and inhibiting differentiation. Here we demonstrate that the histone demethylase JMJD1C functions as a coactivator for RUNX1-RUNX1T1 and is required for its transcriptional program. JMJD1C is directly recruited by RUNX1-RUNX1T1 to its target genes and regulates their expression by maintaining low H3K9 dimethyl (H3K9me2) levels. Analyses in JMJD1C knockout mice also establish a JMJD1C requirement for RUNX1-RUNX1T1's ability to increase proliferation. We also show a critical role for JMJD1C in the survival of multiple human AML cell lines, suggesting that it is required for leukemic programs in different AML cell types through its association with key transcription factors.

Keywords: AML1-ETO; HEB; LYL1; acute myeloid leukemia; histone demethylase; transcription regulation.

Publication types

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

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cell Survival / genetics
  • Core Binding Factor Alpha 2 Subunit / genetics
  • Core Binding Factor Alpha 2 Subunit / metabolism
  • Gene Expression Regulation, Leukemic*
  • Jumonji Domain-Containing Histone Demethylases / genetics
  • Jumonji Domain-Containing Histone Demethylases / metabolism*
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / physiopathology*
  • Mice, Knockout
  • Oxidoreductases, N-Demethylating / genetics
  • Oxidoreductases, N-Demethylating / metabolism*
  • Protein Transport / genetics
  • Transcription Factors / metabolism*


  • Core Binding Factor Alpha 2 Subunit
  • Transcription Factors
  • JMJD1C protein, human
  • JMJD1c protein, mouse
  • Jumonji Domain-Containing Histone Demethylases
  • Oxidoreductases, N-Demethylating

Associated data

  • GEO/GSE63486