Transcriptional activation of mouse mast cell protease-9 by microphthalmia-associated transcription factor
Masaru Murakami1, Teruo Ikeda, Kenji Ogawa
1Laboratory of Molecular Biology, Azabu University School of Veterinary Medicine, Sagamihara, Japan.
Abstract:
We explored transcriptional regulation of mouse mast cell protease-9 (mMCP-9), which is implicated in inflammation of the jejunum during helminth infections and tissue remodeling of the uterus during pregnancy. Transcription was positively regulated by microphthalmia-associated transcription factor (MITF), a member of the basic helix-loop-helix-leucine zipper family that binds to the E-box, a CANNTG sequence. The most significant segment for positive regulation by MITF was nt -183 to -177 of the mMCP-9 promoter, CATCATG, which bound MITF-M. In addition, not only other MITF isoforms but also TFE3, another member of the family, activated mMCP-9 transcription through this nucleotide sequence inserted one base within the E-box.
Insights
Microphthalmia-associated transcription factor (MITF) positively regulates mouse mast cell protease-9 (mMCP-9) transcription. This regulation is crucial for mMCP-9
Area of Science:
- Molecular Biology
- Immunology
- Developmental Biology
Background:
- Mouse mast cell protease-9 (mMCP-9) is involved in helminth-induced jejunal inflammation and uterine tissue remodeling during pregnancy.
- Transcriptional regulation of mMCP-9 is critical for understanding its role in these physiological and pathological processes.
Purpose of the Study:
- To elucidate the transcriptional regulation of mMCP-9.
- To identify the specific transcription factors and DNA sequences involved in mMCP-9 gene expression.
Main Methods:
- Analysis of the mMCP-9 promoter region.
- Electrophoretic mobility shift assays (EMSAs) to study transcription factor binding.
- Reporter gene assays to assess transcriptional activity.
Main Results:
- Microphthalmia-associated transcription factor (MITF) was identified as a positive regulator of mMCP-9 transcription.
- The mMCP-9 promoter region from nucleotide -183 to -177 (CATCATG) was found to be a key binding site for MITF-M.
- Other MITF isoforms and TFE3 also activated mMCP-9 transcription via this E-box-proximal sequence.
Conclusions:
- MITF and TFE3 play significant roles in the transcriptional activation of mMCP-9.
- The identified promoter region and its interaction with MITF are critical for mMCP-9 gene expression in relevant biological contexts.
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