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SUV39H1 interacts with AML1 and abrogates AML1 transactivity. AML1 is methylated in vivo
Soumen Chakraborty1, Kislay Kumar Sinha, Vitalyi Senyuk
1Department of Pathology and The Cancer Center, University of Illinois at Chicago, Chicago, IL 60607, USA.
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.
Insights
The histone methyltransferase SUV39H1 interacts with Acute Myeloid Leukemia 1 (AML1), a key gene regulator. This interaction inhibits AML1
Area of Science:
- Molecular Biology
- Epigenetics
- Hematopoiesis
Background:
- Acute Myeloid Leukemia 1 (AML1) is a crucial DNA-binding protein regulating hematopoietic gene expression.
- AML1 is essential for fetal liver hematopoiesis in mice.
- Previous studies show AML1 interacts with histone acetyltransferases and deacetylases.
Purpose of the Study:
- To investigate the interaction between AML1 and histone methyltransferase SUV39H1.
- To understand how SUV39H1 affects AML1's function in gene regulation.
Main Methods:
- Co-immunoprecipitation assays to detect protein complexes.
- Analysis of AML1 N-terminus and Runt domain involvement.
- Assessment of AML1's DNA-binding and transactivating properties.
Main Results:
- SUV39H1 forms a complex with AML1.
- The interaction requires AML1's N-terminus, including the Runt domain.
- SUV39H1 binding abrogates AML1's DNA-binding and transactivating capabilities.
- AML1's nuclear structure is disrupted upon binding to SUV39H1.
Conclusions:
- SUV39H1 negatively regulates AML1 activity.
- Histone methyltransferases are involved in modulating AML1's gene regulatory functions.
- This interaction provides new insights into epigenetic control of hematopoiesis.