AF4 uses the SL1 components of RNAP1 machinery to initiate MLL fusion- and AEP-dependent transcription.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 26593443.
- Also identified by DOI 10.1038/ncomms9869 and PMC identifier 4673504.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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.
Medical subject headings
- DNA-Binding Proteins
- Histone-Lysine N-Methyltransferase
- Myeloid-Lymphoid Leukemia Protein
- Nuclear Proteins
- Oncogene Proteins, Fusion
- Pol1 Transcription Initiation Complex Proteins
- RNA Polymerase I
- Transcription, Genetic