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Molecular cloning of ESET, a novel histone H3-specific methyltransferase that interacts with ERG transcription factor

Oncogene volume 21, pages 148–152 (2002)Cite this article

Abstract

The ets-related gene erg encodes a transcription factor that is implicated in the control of cell growth and differentiation. To identify interacting partners of ERG, we screened a yeast two-hybrid cDNA library constructed from mouse hematopoietic cells using the N-terminal region of ERG as a bait. We isolated a 4.6 kb full-length mouse cDNA encoding a 1307-amino acid protein migrating as a 180 kD band, which was termed ESET (ERG-associated protein with SET domain). ESET is 92% identical to the human protein SETDB1 (SET domain, bifurcated 1). The interaction between ESET and ERG was supported by in vitro pull-down using glutathione S-transferase (GST) fusion protein, by transfection and co-immunoprecipitation experiments, and by association of endogenous SETDB1 with ERG. Since ESET possesses evolutionarily conserved SET, preSET, and postSET domains implicated in histone methylation, we tested the ability of ESET to methylate core histones. The results of these studies demonstrated that ESET is a histone H3-specific methyltransferase, and that mutations within ESET abolished its methyltransferase activity. Together, these findings raise the possibility that transcription factor ERG may participate in transcriptional regulation through ESET-mediated histone methylation.

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Acknowledgements

We thank Dr Thomas Jenuwein for the myc-SUV39h1 plasmid. This work is supported in part by funds from the Department of Orthopedics and Sports Medicine at the University of Washington and by a New Investigator Grant from the Leukemia Research Foundation (to L Yang). Y Zhang is a V-foundation scholar and work in his lab is supported by NIH (GM63067-01) and ACS (RSG-00-351-01-GMC).

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Authors and Affiliations

  1. Medical Research Service, VA Puget Sound Health Care System, University of Washington, Seattle, 98108, Washington, WA, USA

    Liu Yang, Daniel Y Wu, Howard A Chansky & William H Schubach

  2. Department of Orthopedics, University of Washington, Seattle, 98108, Washington, WA, USA

    Liu Yang & Howard A Chansky

  3. Department of Medicine/Oncology, University of Washington, Seattle, 98108, Washington, WA, USA

    Daniel Y Wu & William H Schubach

  4. Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, 27599, North Carolina, NC, USA

    Li Xia, Hengbin Wang & Yi Zhang

  5. Department of Experimental Transplantation and Immunology, National Cancer Institute, Bethesda, 20892, Maryland, MD, USA

    Dennis D Hickstein

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  1. Liu Yang
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  2. Li Xia
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Correspondence to Yi Zhang.

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Yang, L., Xia, L., Wu, D. et al. Molecular cloning of ESET, a novel histone H3-specific methyltransferase that interacts with ERG transcription factor. Oncogene 21, 148–152 (2002). https://doi.org/10.1038/sj.onc.1204998

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