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AF4 uses the SL1 components of RNAP1 machinery to initiate MLL fusion- and AEP-dependent transcription
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Description
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.
Journal
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- Nature Communications
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Nature Communications 6 8869-, 2015-11-23
Nature Publishing Group
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Keywords
Details 詳細情報について
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- CRID
- 1050564285769822976
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- NII Article ID
- 120005672585
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- ISSN
- 20411723
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- HANDLE
- 2433/201896
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- PubMed
- 26593443
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- Text Lang
- en
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- Article Type
- journal article
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- Data Source
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- IRDB
- Crossref
- CiNii Articles
- KAKEN
- OpenAIRE