NTF3 Is a Novel Target Gene of the Transcription Factor POU3F2 and Is Required for Neuronal Differentiation

Yi Mei J. Lin, I. Lun Hsin, H. Sunny Sun, Shankung Lin, Yen Ling Lai, Hsuan Ying Chen, Ting Yu Chen, Ya Ping Chen, Yi Ting Shen, Hung Ming Wu

研究成果: Article同行評審

12 引文 斯高帕斯(Scopus)

摘要

POU-homeodomain transcription factor POU3F2 is a critical transcription factor that participates in neuronal differentiation. However, little is known about its downstream mediators. Here genome-wide analyses of a human neuronal differentiation cell model, NT2D1, suggested neurotrophin-3 (NTF3), a key mediator of neuronal development during the early neurogenic period, as a putative regulatory target of POU3F2. Western blot, cDNA microarray, and real-time quantitative PCR analyses showed that POU3F2 and NTF3 were upregulated during neuronal differentiation. Next-generation-sequence-based POU3F2 chromatin immunoprecipitation-sequencing and genome-wide in silico prediction demonstrated that POU3F2 binds to the NTF3 promoter during neuronal differentiation. Furthermore, unidirectional deletion or mutation of the binding site of POU3F2 in the NTF3 promoter decreased promoter-driven luciferase activity, indicating that POU3F2 is a positive regulator of NTF3 promoter activity. While NTF3 knockdown resulted in decreased viability and differentiation of NT2D1 cells, and POU3F2 knockdown downregulated NTF3 expression, recombinant NTF3 significantly rescued viable neuronal cells from NTF3- or POU3F2-knockdown cell cultures. Moreover, immunostaining showed colocalization of POU3F2 and NTF3 in developing mouse neurons. Thus, our data suggest that NTF3 is a novel target gene of POU3F2 and that the POU3F2/NTF3 pathway plays a role in the process of neuronal differentiation.

原文English
頁(從 - 到)8403-8413
頁數11
期刊Molecular Neurobiology
55
發行號11
DOIs
出版狀態Published - 2018 十一月 1

All Science Journal Classification (ASJC) codes

  • 神經內科
  • 細胞與分子神經科學

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