JMJD1C is required for the survival of acute myeloid leukemia by functioning as a coactivator for key transcription factors
- Mo Chen1,
- Nan Zhu2,6,
- Xiaochuan Liu3,
- Benoit Laurent4,5,
- Zhanyun Tang1,
- Rowena Eng2,
- Yang Shi4,5,
- Scott A. Armstrong2 and
- Robert G. Roeder1
- 1Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, New York 10065, USA;
- 2Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA;
- 3Department of Microbiology, Biochemistry, and Molecular Genetics, Rutgers University, Newark, New Jersey 07103, USA;
- 4Division of Newborn Medicine, Epigenetics Program, Department of Medicine, Boston Children's Hospital, Boston, Massachusetts 02115, USA;
- 5Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
- Corresponding author: roeder{at}rockefeller.edu
Abstract
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.
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Footnotes
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Supplemental material is available for this article.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.267278.115.
- Received June 11, 2015.
- Accepted September 29, 2015.
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