Gene rearrangements generate MLL fusion genes, which can lead to aggressive leukemia. In most cases, MLL fuses with a gene encoding a component of the AEP (AF4 family/ENL family/P-TEFb) coactivator complex. MLL-AEP fusion proteins constitutively activate their target genes to immortalize haematopoietic progenitors. Here we show that AEP and MLL-AEP fusion proteins activate transcription through selectivity factor 1 (SL1), a core component of the pre-initiation complex (PIC) of RNA polymerase I (RNAP1). The pSER domain of AF4 family proteins associates with SL1 on chromatin and loads TATA-binding protein (TBP) onto the promoter to initiate RNA polymerase II (RNAP2)-dependent transcription. These results reveal a previously unknown transcription initiation mechanism involving AEP and a role for SL1 as a TBP-loading factor in RNAP2-dependent gene activation.

中文翻译：

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AF4使用RNAP1机器的SL1组件来启动MLL融合和AEP依赖的转录。

基因重排产生MLL融合基因，其可导致侵袭性白血病。在大多数情况下，MLL与编码AEP（AF4家族/ ENL家族/ P-TEFb）共激活复合物成分的基因融合。MLL-AEP融合蛋白可组成性地激活其靶基因，以永生造血祖细胞。在这里，我们显示AEP和MLL-AEP融合蛋白通过选择性因子1（SL1）激活转录，选择性因子1是RNA聚合酶I（RNAP1）的预启动复合物（PIC）的核心成分。AF4家族蛋白的pSER结构域与染色质上的SL1缔合，并将TATA结合蛋白（TBP）加载到启动子上，以启动RNA聚合酶II（RNAP2）依赖性转录。