A novel interaction between the proto-oncogene Evi1 and histone methyltransferases, SUV39H1 and G9a.
The transcription factor ecotropic viral integration site 1 (Evi1) is associated with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in patients due to chromosomal aberration of chromosome 3. Here we show that Evi1 interacts with the histone methyltransferase SUV39H1. The interaction requires the N-terminal part of Evi1 and the H3-specific histone methyltransferase domain, SET, of SUV39H1 without Evi1 having an inhibitory effect on SUV39H1 methyltransferase activity. Presence of SUV39H1 enhances Evi1 transcriptional repression in a dose dependent manner. In addition, Evi1 also interacts with another histone methyltransferase, G9a, but not with SET9. Our data establish an epigenetic role of Evi1 in cell transformation by recruiting higher order chromatin remodeling complexes.
Spensberger
Dominik
D
Department of Hematology, Erasmus University Medical Center, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
Delwel
Ruud
R
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000074008:MDS1 and EVI1 Complex Locus Protein; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011496:Protein Methyltransferases; D017434:Protein Structure, Tertiary; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; D000090063:Proto-Oncogene Mas; D012097:Repressor Proteins; D014157:Transcription Factors; C407843:SUV39H1 protein, human; D000076983:Histone Methyltransferases; D008780:Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C540312:SETD7 protein, human