title: Molecular cloning of ESET, a novel histone H3-specific methyltransferase that interacts with ERG transcription factor.
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.
authors.affiliation: Medical Research Service, VA Puget Sound Health Care System, University of Washington, Seattle, Washington, WA 98108, USA.
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.forename: Li
authors.initials: L
authors.lastname: Xia
authors.forename: Daniel Y
authors.initials: DY
authors.lastname: Wu
authors.forename: Hengbin
authors.initials: H
authors.lastname: Wang
authors.forename: Howard A
authors.initials: HA
authors.lastname: Chansky
authors.forename: William H
authors.initials: WH
authors.lastname: Schubach
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Hickstein
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins; D005982:Glutathione Transferase / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000737:chemistry; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D016297:Mutagenesis, Site-Directed; D015513:Oncogene Proteins / Q000378:metabolism*; D011496:Protein Methyltransferases; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism*; D000071230:Transcriptional Regulator ERG; D014162:Transfection; D020798:Two-Hybrid System Techniques
chemical_list: D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C072312:ERG protein, human; D006657:Histones; D015513:Oncogene Proteins; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000071230:Transcriptional Regulator ERG; D000076983:Histone Methyltransferases; D008780:Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D005982:Glutathione Transferase