Regulation of mouse mast cell protease 6 gene expression by transcription factor encoded by the mi locus

Eiichi Morii, Tohru Tsujimura, Tomoko Jippo, Koji Hashimoto, Kimiko Takebayashi, Kumiko Tsujino, Shintaro Nomura, Masayuki Yamamoto, Yukihiko Kitamura

Research output: Contribution to journalArticlepeer-review

106 Citations (Scopus)

Abstract

The mi locus of mice encodes a member of the basic-helixloop-helix- leucine zipper (bHLH-Zip) protein family of transcription factors (hereafter called MITF). Because the expression of the mouse mast cell protease 6 (MMCP- 6) gene is remarkably reduced in mast cells of mi/mi mutant mice, we investigated the effect of MITF on the transcription of the MMCP-6 gene. First, we introduced the normal (+) MITF cDNA into mi/mi cultured mast cells using the retroviral vector. Overexpression of +-MITF but not mi-MITF normalized the expression of the MMCP-6 gene, indicating the involvement of +-MITF in the MMCP-6 gene transactivation. Second, we analyzed the promoter of the MMCP-6 gene by the transient cotransfection assay. The luciferase construct under the control of the MMCP-6 promoter and the cDNA encoding +- MITF or mi-MITF were cotransfected into NIH/3T3 fibroblasts. The coexpression of +-MITF but not mi-MITF increased the luciferase activity 10-fold. We found a CACATG and a CATCTG motif in the MMCP-6 promoter, both of which are generally recognized by bHLH-Zip-type transcription factors. We also found a GACCTG motif that was strongly bound by +-MITF. These three motifs were necessary for the 10-fold transactivation ability of the MMCP-6 promoter by +-MITF. Mutations of each motif significantly reduced the transactivation, suggesting that +-MITF directly transactivated the MMCP-6 gene through these three motifs.

Original languageEnglish
Pages (from-to)2488-2494
Number of pages7
JournalBlood
Volume88
Issue number7
DOIs
Publication statusPublished - 1996 Oct 1

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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