RRC ID 45180
著者 Mino K, Nishimura S, Ninomiya S, Tujii H, Matsumori Y, Tsuchida M, Hosoi M, Koseki K, Wada S, Hasegawa M, Sasaki R, Murakami-Yamaguchi Y, Narita H, Suzuki T, Miyata N, Mizukami T.
タイトル Regulation of tissue factor pathway inhibitor-2 (TFPI-2) expression by lysine-specific demethylase 1 and 2 (LSD1 and LSD2).
ジャーナル Biosci Biotechnol Biochem
Abstract 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.
巻・号 78(6)
ページ 1010-7
公開日 2014-1-1
DOI 10.1080/09168451.2014.910104
PMID 25036127
MeSH Carcinogenesis DNA Methylation / drug effects Endodeoxyribonucleases Enzyme Inhibitors / pharmacology Gene Expression Regulation* / drug effects Gene Knockdown Techniques Glycoproteins / genetics* HEK293 Cells Histone Demethylases / antagonists & inhibitors Histone Demethylases / deficiency Histone Demethylases / genetics Histone Demethylases / metabolism* Histones / metabolism Humans Promoter Regions, Genetic / genetics
IF 1.516
引用数 9
WOS 分野 FOOD SCIENCE & TECHNOLOGY BIOTECHNOLOGY & APPLIED MICROBIOLOGY CHEMISTRY, APPLIED BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 293(RCB1637)