JMJD1C is required for the survival of acute myeloid leukemia by functioning as a coactivator for key transcription factors
2015
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
demethylaseJMJD1C functions as a
coactivatorfor
RUNX1–
RUNX1T1and is required for its transcriptional program. JMJD1C is directly recruited by
RUNX1–
RUNX1T1to 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.
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