Transcriptional Regulation of Basophil-specific Protease Genes by C/EBPα, GATA2, TGF-β Signaling, and Epigenetic Mechanisms

Overview

Journal FEBS Lett

Specialty Biochemistry

Date 2024 Dec 11

PMID 39660487

Authors

Ryotaro Tojima

Kazuki Nagata

Naoto Ito

Kenta Ishii

Takahiro Arai

Tomoka Ito

Kazumi Kasakura

Chiharu Nishiyama

Affiliations

Soon will be listed here.

Abstract

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.

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