Department of Molecular and Cellular Biochemistry, Loyola University Chicago, Stritch School of Medicine, Maywood, IL 60153, USA.
FEBS Lett. 2013 Sep 17;587(18):3038-44. doi: 10.1016/j.febslet.2013.07.034. Epub 2013 Jul 25.
AF9 is known to interact with multiple proteins including activators and repressors of transcription. Our data indicate that other AF9 binding proteins compete with the histone methyltransferase DOT1L for AF9 binding thus diminishing its ability to methylate lysine 79 of histone 3. Specifically, we show that AF9 is part of a protein multimer containing members of Polycomb group (PcG) PRC1 complex, CBX8, RING1B, and BMI1. Interaction with CBX8 precludes AF9-DOT1L binding. Knockdown of CBX8 with short-hairpin RNA (shRNA) leads to decreased expression of the AF9 target gene ENaCα. In contrast, CBX8 overexpression results in increased ENaCα mRNA levels and this effect can be partially overcome by co-overexpression of AF9.
AF9 已知与多种蛋白质相互作用,包括转录的激活剂和抑制剂。我们的数据表明,其他与 AF9 结合的蛋白质与组蛋白甲基转移酶 DOT1L 竞争,从而降低其甲基化组蛋白 H3 赖氨酸 79 的能力。具体来说,我们表明 AF9 是含有多梳抑制复合物 (PcG) PRC1 复合物、CBX8、RING1B 和 BMI1 成员的蛋白质多聚体的一部分。与 CBX8 的相互作用阻止了 AF9-DOT1L 的结合。用短发夹 RNA (shRNA) 敲低 CBX8 导致 AF9 靶基因 ENaCα 的表达减少。相比之下,CBX8 的过表达导致 ENaCα mRNA 水平增加,并且这种效应可以通过共表达 AF9 部分克服。