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タイトル: | Regulation of alternative polyadenylation by Nkx2-5 and Xrn2 during mouse heart development |
著者: | Nimura, Keisuke Yamamoto, Masamichi Takeichi, Makiko Saga, Kotaro Takaoka, Katsuyoshi Kawamura, Norihiko Nitta, Hirohisa Nagano, Hiromichi Ishino, Saki Tanaka, Tatsuya Schwartz, Robert J. Aburatani, Hiroyuki Kaneda, Yasufumi |
著者名の別形: | 山本, 正道 |
発行日: | 22-Jun-2016 |
出版者: | eLife Sciences Publications Ltd |
誌名: | eLife |
巻: | 5 |
論文番号: | e16030 |
抄録: | Transcription factors organize gene expression profiles by regulating promoter activity. However, the role of transcription factors after transcription initiation is poorly understood. Here, we show that the homeoprotein Nkx2-5 and the 5'-3' exonuclease Xrn2 are involved in the regulation of alternative polyadenylation (APA) during mouse heart development. Nkx2-5 occupied not only the transcription start sites (TSSs) but also the downstream regions of genes, serving to connect these regions in primary embryonic cardiomyocytes (eCMs). Nkx2-5 deficiency affected Xrn2 binding to target loci and resulted in increases in RNA polymerase II (RNAPII) occupancy and in the expression of mRNAs with long 3‘untranslated regions (3' UTRs) from genes related to heart development. siRNA-mediated suppression of Nkx2-5 and Xrn2 led to heart looping anomaly. Moreover, Nkx2-5 genetically interacts with Xrn2 because Nkx2-5+/-Xrn2+/-, but neither Nkx2-5+/-nor Xrn2+/-, newborns exhibited a defect in ventricular septum formation, suggesting that the association between Nkx2-5 and Xrn2 is essential for heart development. Our results indicate that Nkx2-5 regulates not only the initiation but also the usage of poly(A) sites during heart development. Our findings suggest that tissue-specific transcription factors is involved in the regulation of APA. |
著作権等: | © Nimura et al. opyright Nimura et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. |
URI: | http://hdl.handle.net/2433/218633 |
DOI(出版社版): | 10.7554/eLife.16030.001 |
出現コレクション: | 学術雑誌掲載論文等 |
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