Inhibitory effect of the transcription factor encoded by the mutant mi microphthalmia allele on transactivation of mouse mast cell protease 7 gene

Blood ◽  
2001 ◽  
Vol 97 (3) ◽  
pp. 645-651 ◽  
Author(s):  
Hideki Ogihara ◽  
Eiichi Morii ◽  
Dae-Ki Kim ◽  
Keisuke Oboki ◽  
Yukihiko Kitamura
Keyword(s):  
Transcription Factor ◽  
Mast Cell ◽  
Inhibitory Effect ◽  
Chromosome 17 ◽  
Binding Motif ◽  
Mast Cell Protease ◽  
Coding Regions ◽  
Helix Loop Helix ◽  
Negative Effect ◽  
Mouse Mast Cell

Abstract The transcription factor encoded by the mi locus (MITF) is a transcription factor of the basic-helix-loop-helix zipper protein family. Mice of mi/mi genotype express a normal amount of abnormal MITF, whereas mice oftg/tg genotype do not express any MITFs due to the transgene insertional mutation. The effect of normal (+) and mutant (mi) MITFs on the expression of mouse mast cell protease (MMCP) 6 and 7 was examined. Both MMCP-6 and MMCP-7 are tryptases, and their coding regions with high homology are closely located on chromosome 17. Both MMCP-6 and MMCP-7 genes are expressed in normal cultured mast cells (+/+ CMCs). Although the transcription of MMCP-6 gene was severely suppressed in bothmi/mi and tg/tg CMCs, that of MMCP-7 gene was severely suppressed only in mi/mi CMCs. The study identified the most significant segment for the transcription in the 5′ flanking region of MMCP-7 gene. Unexpectedly, no CANNTG motifs were found that are recognized and bound by +-MITF in this segment. Instead, there was an AP-1 binding motif, and binding of c-Jun to the AP-1 motif significantly enhanced the transcription of MMCP-7 gene. The complex formation of c-Jun with either +-MITF ormi-MITF was demonstrated. The binding of +-MITF to c-Jun enhanced the transactivation of MMCP-7 gene, and that ofmi-MITF suppressed the transactivation. Although the former complex was located only in the nucleus, the latter complex was predominantly found in the cytoplasm. The negative effect ofmi-MITF on the transcription of MMCP-7 gene appeared to be executed through the interaction with c-Jun.

Inhibitory Effect of the Transcription Factor Encoded by themi Mutant Allele in Cultured Mast Cells of Mice

Blood ◽  
1999 ◽  
Vol 93 (4) ◽  
pp. 1189-1196 ◽  
Author(s):  
Akihiko Ito ◽  
Eiichi Morii ◽  
Dae-Ki Kim ◽  
Tatsuki R. Kataoka ◽  
Tomoko Jippo ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Mast Cells ◽  
Leucine Zipper ◽  
Tryptophan Hydroxylase ◽  
Cdna Probe ◽  
Inhibitory Effect ◽  
Northern Analysis ◽  
Helix Loop Helix ◽  
Genes Encoding ◽  
Mouse Mast Cell

The mi locus of mice encodes a transcription factor of the basic-helix-loop-helix-leucine zipper protein family (MITF). The MITF encoded by the mutant mi allele (mi-MITF) deletes 1 of 4 consecutive arginines in the basic domain. The mice of mi/migenotype express mi-MITF, whereas the mice of tg/tggenotype have a transgene at the 5′ flanking region of themi gene and do not express any MITF. To investigate the function of mi-MITF in cultured mast cells (CMCs), we took two approaches. First, mRNA obtained from mi/mi CMCs ortg/tg CMCs was subtracted from complementary (c) DNA library of normal (+/+) CMCs, and the (+/+-mi/mi) and (+/+-tg/tg) subtraction libraries were obtained. When the number of clones that hybridized more efficiently with +/+ CMC cDNA probe than with mi/mi or tg/tg CMC cDNA probe was compared using Southern analysis, the number was larger in the (+/+-mi/mi) library than in the (+/+-tg/tg) library. Second, we compared mRNA expression of six genes betweenmi/mi and tg/tg CMCs by Northern analysis. The transcription of three genes encoding mouse mast cell proteases was impaired in both mi/mi and tg/tg CMCs. On the other hand, the transcription of three genes encoding c-kit receptor, tryptophan hydroxylase, and granzyme B was markedly reduced inmi/mi CMCs, but the reduction was significantly smaller intg/tg CMCs. These results indicated the inhibitory effect ofmi-MITF on the transactivation of particular genes in CMCs.

scholarly journals Synergy of PEBP2/CBF with mi transcription factor (MITF) for transactivation of mouse mast cell protease 6 gene

Oncogene ◽  
1999 ◽  
Vol 18 (32) ◽  
pp. 4632-4639 ◽  
Author(s):  
Hideki Ogihara ◽  
Tomohiko Kanno ◽  
Eiichi Morii ◽  
Dae-Ki Kim ◽  
Young-Mi Lee ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Mast Cell ◽  
Mast Cell Protease ◽  
Mouse Mast Cell

Deficient Transcription of Mouse Mast Cell Protease 4 Gene in Mutant Mice of mi/mi Genotype

Blood ◽  
1999 ◽  
Vol 93 (6) ◽  
pp. 1942-1950 ◽  
Author(s):  
Tomoko Jippo ◽  
Young-Mi Lee ◽  
Yee Katsu ◽  
Kumiko Tsujino ◽  
Eiichi Morii ◽  
...  
Keyword(s):  
Mast Cell ◽  
Leucine Zipper ◽  
Granzyme B ◽  
Mutant Mice ◽  
Cathepsin G ◽  
Mast Cell Protease ◽  
Helix Loop Helix ◽  
Regulation Mechanisms ◽  
The Difference ◽  
Mouse Mast Cell

The mi locus encodes a member of the basic-helix-loop-helix-leucine zipper (bHLH-Zip) protein family of transcription factors (hereafter called MITF). We reported that expression of the mouse mast cell protease 5 (MMCP-5) and MMCP-6 genes were deficient in cultured mast cells (CMC) derived from mutant mice ofmi/mi genotype. Despite the reduced expression of both MMCP-5 and MMCP-6, their regulation mechanisms were different. Because MMCP-5 is a chymase and MMCP-6 a tryptase, there was a possibility that the difference in regulation mechanisms was associated with their different characteristics as proteases. We compared the regulation mechanisms of another chymase, MMCP-4, with those of MMCP-5 and MMCP-6. The expression of the MMCP-4 gene was also deficient in mi/mi CMC. The overexpression of the normal (+) MITF but not of mi-MITF normalized the poor expression of the MMCP-4 gene in mi/mi CMC, indicating the involvement of +-MITF in transactivation of the MMCP-4 gene. Although MMCP-4 is chymase as MMCP-5, the regulation of MMCP-4 expression was more similar to MMCP-6 than to MMCP-5. We also showed the deficient expression of granzyme B and cathepsin G genes inmi/mi CMC. Genes encoding granzyme B, cathepsin G, MMCP-4, and MMCP-5 are located on chromosome 14. Because all these genes showed deficient expression in mi/mi CMC, there is a possibility that MITF might regulate the expression of these genes through a locus control region.

scholarly journals Abnormal Expression of Mouse Mast Cell Protease 5 Gene in Cultured Mast Cells Derived From Mutant mi/mi Mice

Blood ◽  
1997 ◽  
Vol 90 (8) ◽  
pp. 3057-3066 ◽  
Author(s):  
Eiichi Morii ◽  
Tomoko Jippo ◽  
Tohru Tsujimura ◽  
Koji Hashimoto ◽  
Dae-Ki Kim ◽  
...  
Keyword(s):  
Mast Cell ◽  
Transcription Factors ◽  
Mast Cells ◽  
Promoter Region ◽  
Leucine Zipper ◽  
Consensus Sequence ◽  
Mast Cell Protease ◽  
Helix Loop Helix ◽  
Regulation Mechanisms ◽  
Mouse Mast Cell

Abstract Mast cells contain a lot of mast cell-specific proteases. We have reported that the expression of mouse mast cell protease 6 (MMCP-6) is remarkably reduced in both cultured mast cells (CMCs) and skin mast cells of mi/mi mutant mice. In the present study, we found that the expression of MMCP-5 was reduced in CMCs but not in skin mast cells of mi/mi mice, and we compared the regulation mechanisms of MMCP-5 with those of MMCP-6. The mi locus encodes a member of the basic-helix-loop-helix-leucine zipper (bHLH-Zip) protein family of transcription factors (hereafter called MITF ). The consensus sequence recognized and bound by bHLH-Zip transcription factors is CANNTG. The overexpression of the normal (+) MITF but not of mi-MITF normalized the poor expression of the MMCP-5 gene in mi/mi CMCs, indicating the involvement of +-MITF in transactivation of the MMCP-5 gene. Although +-MITF directly bound CANNTG motifs in the promoter region of the MMCP-6 gene and transactivated it, the binding of +-MITF to the CAGTTG motif in the promoter region of the MMCP-5 gene was not detectable. The +-MITF appeared to regulate the transactivation of the MMCP-5 gene indirectly. Moreover, addition of stem cell factor to the medium normalized the expression of the MMCP-5 but not of the MMCP-6 gene in mi/mi CMCs. Despite the significant reduction of both MMCP-5 and MMCP-6 expressions in mi/mi CMCs, their regulation mechanisms appeared to be different.

Location of the mouse mast cell protease 7 gene (Mcpt7) to Chromosome 17

1994 ◽  
Vol 5 (10) ◽  
pp. 656-657 ◽  
Author(s):  
M. F. Gurish ◽  
K. R. Johnson ◽  
M. J. Webster ◽  
R. L. Stevens ◽  
J. H. Nadeau
Keyword(s):  
Mast Cell ◽  
Chromosome 17 ◽  
Mast Cell Protease ◽  
Mouse Mast Cell

Inhibitory Effect of the Transcription Factor Encoded by themi Mutant Allele in Cultured Mast Cells of Mice

Blood ◽  
1999 ◽  
Vol 93 (4) ◽  
pp. 1189-1196 ◽  
Author(s):  
Akihiko Ito ◽  
Eiichi Morii ◽  
Dae-Ki Kim ◽  
Tatsuki R. Kataoka ◽  
Tomoko Jippo ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Mast Cells ◽  
Leucine Zipper ◽  
Tryptophan Hydroxylase ◽  
Cdna Probe ◽  
Inhibitory Effect ◽  
Northern Analysis ◽  
Helix Loop Helix ◽  
Genes Encoding ◽  
Mouse Mast Cell

Abstract The mi locus of mice encodes a transcription factor of the basic-helix-loop-helix-leucine zipper protein family (MITF). The MITF encoded by the mutant mi allele (mi-MITF) deletes 1 of 4 consecutive arginines in the basic domain. The mice of mi/migenotype express mi-MITF, whereas the mice of tg/tggenotype have a transgene at the 5′ flanking region of themi gene and do not express any MITF. To investigate the function of mi-MITF in cultured mast cells (CMCs), we took two approaches. First, mRNA obtained from mi/mi CMCs ortg/tg CMCs was subtracted from complementary (c) DNA library of normal (+/+) CMCs, and the (+/+-mi/mi) and (+/+-tg/tg) subtraction libraries were obtained. When the number of clones that hybridized more efficiently with +/+ CMC cDNA probe than with mi/mi or tg/tg CMC cDNA probe was compared using Southern analysis, the number was larger in the (+/+-mi/mi) library than in the (+/+-tg/tg) library. Second, we compared mRNA expression of six genes betweenmi/mi and tg/tg CMCs by Northern analysis. The transcription of three genes encoding mouse mast cell proteases was impaired in both mi/mi and tg/tg CMCs. On the other hand, the transcription of three genes encoding c-kit receptor, tryptophan hydroxylase, and granzyme B was markedly reduced inmi/mi CMCs, but the reduction was significantly smaller intg/tg CMCs. These results indicated the inhibitory effect ofmi-MITF on the transactivation of particular genes in CMCs.

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

Blood ◽  
1996 ◽  
Vol 88 (7) ◽  
pp. 2488-2494 ◽  
Author(s):  
E Morii ◽  
T Tsujimura ◽  
T Jippo ◽  
K Hashimoto ◽  
K Takebayashi ◽  
...  
Keyword(s):  
Mast Cell ◽  
Transcription Factors ◽  
Mast Cells ◽  
Leucine Zipper ◽  
Luciferase Activity ◽  
Mast Cell Protease ◽  
Helix Loop Helix ◽  
3T3 Fibroblasts ◽  
Mouse Mast Cell ◽  
Nih 3T3

The mi locus of mice encodes a member of the basic-helix-loop-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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