||AF4 uses the SL1 components of RNAP1 machinery to initiate MLL fusion- and AEP-dependent transcription
Okuda, Hiroshi ,
Kanai, Akinori ,
Ito, Shinji ,
Matsui, HirotakaYokoyama, Akihiko
62015-11-23 , Nature Publishing Group
難治性の白血病が発症するメカニズムの解明に成功 －新たな創薬に期待－. 京都大学プレスリリース. 2015-11-24.
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.