Spensberger Dominik, Delwel Ruud
Department of Hematology, Erasmus University Medical Center, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
FEBS Lett. 2008 Aug 6;582(18):2761-7. doi: 10.1016/j.febslet.2008.06.056. Epub 2008 Jul 11.
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.
转录因子嗜亲性病毒整合位点1（Evi1）因3号染色体的染色体畸变而与患者的急性髓性白血病（AML）和骨髓增生异常综合征（MDS）相关。在此我们表明，Evi1与组蛋白甲基转移酶SUV39H1相互作用。这种相互作用需要Evi1的N端部分以及SUV39H1的H3特异性组蛋白甲基转移酶结构域SET，而Evi1对SUV39H1甲基转移酶活性没有抑制作用。SUV39H1的存在以剂量依赖的方式增强Evi1的转录抑制作用。此外，Evi1还与另一种组蛋白甲基转移酶G9a相互作用，但不与SET9相互作用。我们的数据通过招募高阶染色质重塑复合物确立了Evi1在细胞转化中的表观遗传作用。
