SUV39H1 interacts with AML1 and abrogates AML1 transactivity. AML1 is methylated in vivo.
Acute myeloid leukemia 1 (AML1) belongs to a family of DNA-binding proteins highly conserved through evolution. AML1 regulates the expression of several hematopoietic genes and is essential for murine fetal liver hematopoiesis. We report here that the histone methyltransferase SUV39H1, a mammalian ortholog of the Drosophila melanogaster SU(VAR) 3-9, forms complex with AML1. SUV39H1 methylates lysine 9 of the histone protein H3 leading to the formation of the high-affinity binding site on chromatin for proteins of the heterochromatin protein 1 family (HP1). The interaction of AML1 with SUV39H1 requires the N-terminus of AML1 where the Runt domain is located. Binding of AML1 to SUV39H1 abrogates the transactivating and DNA-binding properties of AML1 and dissociates the net-like nuclear structure of AML1. It has been reported that AML1 is capable of interaction with histone acetyl transferases (CBP, p300, and MOZ) and with component of the histone deacetylase complex (Sin3), and that the interaction with these coregulators affects the strength of AML1 in promoter regulation. Our data suggest that other enzymes are also involved in gene regulation by AML1 activity by modulating the affinity of AML1 for DNA.
Chakraborty
Soumen
S
Department of Pathology and The Cancer Center, University of Illinois at Chicago, Chicago, IL 60607, USA.
Sinha
Kislay Kumar
KK
Senyuk
Vitalyi
V
Nucifora
Giuseppina
G
D016475:3T3 Cells; D000818:Animals; D050676:Core Binding Factor Alpha 2 Subunit; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism*; D051379:Mice; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011518:Proto-Oncogene Proteins; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; C493726:Runx1 protein, mouse; D014157:Transcription Factors; D004247:DNA; C498700:Suv39h1 protein, mouse; D008780:Methyltransferases; D016186:Receptor, Macrophage Colony-Stimulating Factor