TY - JOUR TI - Regulation of alternative polyadenylation by Nkx2-5 and Xrn2 during mouse heart development AU - Nimura, Keisuke AU - Yamamoto, Masamichi AU - Takeichi, Makiko AU - Saga, Kotaro AU - Takaoka, Katsuyoshi AU - Kawamura, Norihiko AU - Nitta, Hirohisa AU - Nagano, Hiromichi AU - Ishino, Saki AU - Tanaka, Tatsuya AU - Schwartz, Robert J AU - Aburatani, Hiroyuki AU - Kaneda, Yasufumi A2 - Proudfoot, Nick J VL - 5 PY - 2016 DA - 2016/06/22 SP - e16030 C1 - eLife 2016;5:e16030 DO - 10.7554/eLife.16030 UR - https://doi.org/10.7554/eLife.16030 AB - 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. KW - transcription factors KW - gene expression KW - development JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -