Analysis on the promoter region of exon IV brain-derived neurotrophic factor in NG108-15 cells

Yusuke Takeuchi, Eishichi Miyamoto, Kohji Fukunaga

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

We have reported that the nuclear isoforms of Ca2+/calmodulin-dependent protein kinase II (CaM KII) are involved in the expression of the exon IV-containing brain-derived neurotrophic factor (BDNF) mRNA. We document here the cis-elements and transcription factors responsive to CaM KII in the activation of the promoter upstream of the exon IV (exon IV-BDNF promoter). Effects of constitutively active mutants of CaM KIV, MAPK kinase kinase (MEKK) and protein kinase A (PKA) on the exon IV-BDNF promoter activity were also evaluated by transfection and luciferase assay. The exon IV-BDNF promoter activity was increased by transfection with CaM KII, MEKK and PKA, but not by CaM KIV. Deletion and mutational analysis of the promoter revealed that the region between nucleotides -56 and -27 was responsive to CaM KII, which contained a CCAAT-box in the region between nucleotides -56 and -43. Expression of C/EBPβ increased the promoter activity and potentiated the effects of CaM KII. The region between nucleotides -79 and -56 was responsive to MEKK, in which both a GA-rich sequence and a GC-box were included. Expression of Sp1 increased the promoter activity, which was further enhanced by transfection with MEKK. The region between nucleotides -43 and -27 was responsive to both PKA and CaM KII, but the transcription factors involved in the region remained unclear. These results suggest that the promoter of the exon IV-BDNF is at least regulated by CaM KII, MEKK and PKA, and that C/EBP/β and Sp1 are potential transcription factors activated by CaM KII and MEKK, respectively.

Original languageEnglish
Pages (from-to)67-79
Number of pages13
JournalJournal of Neurochemistry
Volume83
Issue number1
DOIs
Publication statusPublished - 2002 Oct
Externally publishedYes

Keywords

  • Brain-derived neurotrophic factor
  • C/EBPβ
  • Ca/calmodulin-dependent protein kinase II
  • MEKK
  • Protein kinase A
  • Sp1

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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