TY - JOUR
T1 - Regulation of mouse mast cell protease 6 gene expression by transcription factor encoded by the mi locus
AU - Morii, Eiichi
AU - Tsujimura, Tohru
AU - Jippo, Tomoko
AU - Hashimoto, Koji
AU - Takebayashi, Kimiko
AU - Tsujino, Kumiko
AU - Nomura, Shintaro
AU - Yamamoto, Masayuki
AU - Kitamura, Yukihiko
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 1996/10/1
Y1 - 1996/10/1
N2 - 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.
AB - 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.
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U2 - 10.1182/blood.v88.7.2488.bloodjournal8872488
DO - 10.1182/blood.v88.7.2488.bloodjournal8872488
M3 - Article
C2 - 8839840
AN - SCOPUS:0029822177
VL - 88
SP - 2488
EP - 2494
JO - Blood
JF - Blood
SN - 0006-4971
IS - 7
ER -