Regulation of tissue factor pathway inhibitor-2 (TFPI-2) expression by lysine-specific demethylase 1 and 2 (LSD1 and LSD2)
| Autor: | Satoshi Nishimura, Miho Hosoi, Koshiki Mino, Naoki Miyata, Shuichi Wada, Tamio Mizukami, Yukie Murakami-Yamaguchi, Shogo Ninomiya, Ryuzo Sasaki, Hiroshi Tujii, Hiroshi Narita, Yasumasa Matsumori, Takayoshi Suzuki, Koichi Koseki, Makoto Hasegawa, Mie Tsuchida |
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| Rok vydání: | 2014 |
| Předmět: |
animal structures
Carcinogenesis Applied Microbiology and Biotechnology Biochemistry Analytical Chemistry Histones Epigenetics of physical exercise Histone methylation Humans Cancer epigenetics Enzyme Inhibitors education Promoter Regions Genetic Molecular Biology Epigenomics Glycoproteins Histone Demethylases education.field_of_study Endodeoxyribonucleases biology Organic Chemistry General Medicine DNA Methylation Tissue-factor-pathway inhibitor 2 HEK293 Cells Gene Expression Regulation Histone methyltransferase Gene Knockdown Techniques DNA methylation Cancer research biology.protein Demethylase Biotechnology |
| Zdroj: | Bioscience, biotechnology, and biochemistry. 78(6) |
| ISSN: | 1347-6947 |
| Popis: | Tissue factor pathway inhibitor-2 (TFPI-2) is a major inhibitor of extracellular matrix degradation. Decreases in TFPI-2 contribute to malignant tumor cell production, and TFPI-2 is a presumed tumor suppressor. TFPI-2 gene transcription is regulated by two epigenetic mechanisms: DNA methylation of the promoter and K4 methylation of histone 3 (H3). Lysine-specific demethylase 1 (LSD1) and LSD2 demethylate H3K4me2/1. LSD1 has been implicated in TFPI-2 regulation through both epigenetic mechanisms, but the involvement of LSD2 remains unknown. We prepared a monoclonal anti-LSD2 antibody that clearly distinguishes LSD2 from LSD1. Knockdown of LSD1 or LSD2 by siRNAs increased TFPI-2 protein and mRNA. Simultaneous knockdown of both LSD1 and LSD2 showed additive effects. Bisulfite sequencing revealed that CpG sites in the TFPI-2 promoter region were unmethylated. These results indicate that LSD2 also contributes to TFPI-2 regulation through histone modification, and that further studies of the involvement of LSD2 in tumor malignancy are warranted. |
| Databáze: | OpenAIRE |
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