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タイトル: | AF4 uses the SL1 components of RNAP1 machinery to initiate MLL fusion- and AEP-dependent transcription |
著者: | Okuda, Hiroshi Kanai, Akinori Ito, Shinji Matsui, Hirotaka Yokoyama, Akihiko |
著者名の別形: | 奥田, 博史 横山, 明彦 |
キーワード: | Biological sciences Cancer Molecular biology |
発行日: | 23-Nov-2015 |
出版者: | Nature Publishing Group |
誌名: | Nature Communications |
巻: | 6 |
論文番号: | 8869 |
抄録: | 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. |
記述: | 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. |
著作権等: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
URI: | http://hdl.handle.net/2433/201896 |
DOI(出版社版): | 10.1038/ncomms9869 |
PubMed ID: | 26593443 |
関連リンク: | https://www.kyoto-u.ac.jp/ja/research-news/2015-11-24 |
出現コレクション: | 学術雑誌掲載論文等 |
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