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SUV39H1 interacts with AML1 and abrogates AML1 transactivity. AML1 is methylated in vivo

Oncogene volume 22, pages 5229–5237 (2003)Cite this article

Abstract

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.

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Acknowledgements

We thank Dr T Jenuwein, Austria for the (Myc)3-SUV39H1 construct. This work was supported by NIH-NCI Grants CA72675 and CA96448 (GN). GN is a scholar of the Leukemia and Lymphoma Society.

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  1. Contributed equally to this work

Authors and Affiliations

  1. Department of Pathology and The Cancer Center, University of Illinois at Chicago, Chicago, IL, USA

    Soumen Chakraborty, Kislay Kumar Sinha, Vitalyi Senyuk & Giuseppina Nucifora

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  1. Soumen Chakraborty
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  2. Kislay Kumar Sinha
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  3. Vitalyi Senyuk
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  4. Giuseppina Nucifora
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Correspondence to Giuseppina Nucifora.

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Chakraborty, S., Sinha, K., Senyuk, V. et al. SUV39H1 interacts with AML1 and abrogates AML1 transactivity. AML1 is methylated in vivo. Oncogene 22, 5229–5237 (2003). https://doi.org/10.1038/sj.onc.1206600

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