Alternative splicing of<i>Mef2c</i>promoted by Fox‐1 during neural differentiation in P19 cells

Genes to Cells - Tập 15 Số 3 - Trang 255-267 - 2010
Nor Hakimah Ab Hakim1,2, Toshiki Kounishi1,2, AHM Khurshid Alam1,2, Toshifumi Tsukahara1, Hitoshi Suzuki1
1Center for Nano Materials Technology, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Nomi, Ishikawa 923-1211, Japan
2Graduate School of Materials Science, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Nomi, Ishikawa 923-1211, Japan

Tóm tắt

Mef2c protein is one of the MADS‐box type transcription factors involved in muscular differentiation and synaptic formation. Previously, it has been reported that theMef2cgene is responsible for three alternative splicing regulations. Here, we investigated the alternative splicing variants ofMef2cduring neural differentiation of P19 cells and during cardio muscular differentiation of P19 clone 6 (P19CL6). We detected that twoMef2cmRNA isoforms, using exon α1 with and without the γ region at exon 10, are mainly produced in immature P19 cells. Remarkably,Mef2cisoforms containing exon β specifically appeared in the neural cell stage. Because most transcripts contain exon β in the neural cell stage and in the brain, this suggests that the alternative splicing of exon β is highly regulated. Among known regulators, Fox‐1 was specifically expressed in the neural cell stage in correlation withMef2cexon β. Fox‐1 promoted exon β inclusion in transfection experiments usingMef2cβ minigene. Moreover, we found that the promotion required RNA‐binding activity of Fox‐1 and GCAUG sequence located in adjacent intron of exon β. Taken together, our results suggest that Fox‐1, expressed specifically in the neural cell stage, promotedMef2cexon β inclusion via the GCAUG.

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Genes to Cells

Tập 15 Số 3

255-267

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