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  • Original Article
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RUNX1 associates with histone deacetylases and SUV39H1 to repress transcription

Oncogene volume 25, pages 5777–5786 (2006)Cite this article

Abstract

RUNX1 (AML1) is a gene that is frequently disrupted by chromosomal translocations in acute leukemia. Like its Drosophila homolog Runt, RUNX1 both activates and represses transcription. Both Runt and RUNX1 are required for gene silencing during development and a central domain of RUNX1, termed repression domain 2 (RD2), was defined as being required for transcriptional repression and for the silencing of CD4 during T-cell maturation in thymic organ cultures. Although transcriptional co-repressors are known to contact other repression domains in RUNX1, the factors that bind to RD2 had not been defined. Therefore, we tested whether RD2 contacts histone-modifying enzymes that may mediate both repression and gene silencing. We found that RD2 contacts SUV39H1, a histone methyltransferase, via two motifs and that endogenous Suv39h1 associates with a Runx1-regulated repression element in murine erythroleukemia cells. In addition, one of these SUV39H1-binding motifs is also sufficient for binding to histone deacetylases 1 and 3, and both of these domains are required for full RUNX1-mediated transcriptional repression. The association between RUNX1, histone deacetylases and SUV39H1 provides a molecular mechanism for repression and possibly gene silencing mediated by RUNX1.

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Acknowledgements

We thank members of the Hiebert lab for critical evaluation of the manuscript. We thank the Vanderbilt-Ingram Cancer Center and the VICC DNA sequencing core for support. This work was supported by NIH/NCI grants RO1-CA64140, RO1-CA77274, and RO1-87549 (SWH), RO1-HL49118 (SJB), a Merit Review Award from the Department of Veterans Affairs (SJB), and a Center grant from the National Cancer Institute (CA68485). BJI was a fellow of the Leukemia and Lymphoma Society of America.

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Author notes

  1. E Reed-Inderbitzin

    Present address: University of Oregon Health Sciences Center, Beaverton, OR, USA

  2. B Lutterbach

    Present address: Merck Inc., West Point, PA, USA

  3. K L Durst-Goodwin

    Present address: Indiana University School of Medicine, Indianapolis, IN, USA

  4. B J Irvin

    Present address: The Blood Center of Wisconsin, Milwaukee, WI, USA

  5. E Reed-Inderbitzin, I Moreno-Miralles and S K Vanden-Eynden: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA

    E Reed-Inderbitzin, I Moreno-Miralles, S K Vanden-Eynden, B Lutterbach, K L Durst-Goodwin, K S Luce, B J Irvin & S W Hiebert

  2. Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA

    J Xie & S J Brandt

  3. Stanford University Medical School, Palo Alto, CA, USA

    M L Cleary

  4. Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA

    S J Brandt

  5. Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN, USA

    S J Brandt

  6. Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA

    S J Brandt & S W Hiebert

  7. Tennessee Valley VA Healthcare System, Nashville, TN, USA

    S J Brandt

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  1. E Reed-Inderbitzin
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Correspondence to S W Hiebert.

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Reed-Inderbitzin, E., Moreno-Miralles, I., Vanden-Eynden, S. et al. RUNX1 associates with histone deacetylases and SUV39H1 to repress transcription. Oncogene 25, 5777–5786 (2006). https://doi.org/10.1038/sj.onc.1209591

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