Transcriptional regulation of basophil‐specific protease genes by C/ <scp>EBPα</scp> , <scp>GATA2</scp> , <scp>TGF</scp> ‐β signaling, and epigenetic mechanisms
Basophils and mast cells (MCs) play an important role in immune responses against allergens and parasitic infection. To elucidate the mechanisms that determine the commitment between basophils and mast cell (MCs), transcription factors and epigenetic modifications regulating the gene expression of basophil-specific enzymes, Mcpt8 and Mcpt11, were analyzed using bone marrow-derived (BM) cells containing basophils and MCs. Knockdown (KD) and overexpression experiments revealed that the transcription factor C/EBPα positively regulated the gene expression of Mcpt8 and Prss34 (encoding Mcpt11). Cebpa, Mcpt8, and Prss34 mRNAs levels were upregulated by histone deacetylases and downregulated by DNA methyltransferases. Gata2 KD significantly reduced the mRNA levels of Mcpt8 and Prss34, while TGF-β treatment increased those of Mcpt8 and Prss34. These results show that basophil-specific protease genes were transactivated by C/EBPα, GATA2, and TGF-β signaling and modified with epigenetic regulation.
Authors
- Naoto Ito (ORCID: https://orcid.org/0000-0002-6318-114X)
- Kazuki Nagata (ORCID: https://orcid.org/0000-0002-0100-4199)
- Takahiro Arai (ORCID: https://orcid.org/0000-0003-0201-8207)
- Chiharu Nishiyama (ORCID: https://orcid.org/0000-0002-4082-9097)
- Tomoka Ito (ORCID: https://orcid.org/0009-0001-7281-6928)
- Kazumi Kasakura (ORCID: https://orcid.org/0000-0002-4412-3737)
- Ryotaro Tojima
- Kenta Ishii
Institutions
- Tokyo University of Science (JP)
Publication Details
- Journal
- FEBS Letters
- Published
- 2024-12-11
- DOI
- https://doi.org/10.1002/1873-3468.15069
- Citations
- 3
- Primary Topic
- Mast cells and histamine
- Type
- article
- Field-Weighted Citation Impact
- 0.72
Funders
- Tojuro Iijima Foundation for Food Science and Technology
- Mishima Kaiun Memorial Foundation
- Japan Society for the Promotion of Science