Chen Wen, Obara Masanobu, Ishida Yuji, Suzuki Ken-ichi, Yoshizato Katsutoshi
Department of Biological Science, Graduate School of Science, Hiroshima University, Kagamiyama 1-3-1, Higashihiroshima, Hiroshima 739-8526, Japan.
Dev Growth Differ. 2007 May;49(4):325-34. doi: 10.1111/j.1440-169X.2007.00927.x.
The thyroid hormone receptor (THR) is a member of the nuclear transcription factor and plays a central role in regulating anuran metamorphosis. Previous studies with mammalian cells have suggested that THR is involved in chromatin remodeling through histone methylation. In the present study, we cloned cDNA of lysine-specific demethylase gene, xLSD1, from Xenopus laevis and examined its expression in relation to metamorphosis. Overexpression of xLSD1 in A6 cells, a Xenopus laevis cell line, resulted in the decrease of methylation status of lysine residues of histone H3, indicating that the protein of cloned xLSD1 was functionally active. The expression of LSD1 at mRNA levels was up-regulated in the body skin and the intestine during natural and thyroid hormone-induced metamorphosis. Larval epidermal basal cells and intestinal epithelial cells at the premetamorphic stage were identified as the xLSD1-expressing cells. At the metamorphic climax stage the progenitor cells of adult epidermal basal cells also expressed xLSD1, whereas those of the adult intestinal epithelial cells did not. We propose that LSD1 participates in the regulation of metamorphosis through THR- or another transcriptional factor-induced chromatin remodeling.
甲状腺激素受体（THR）是核转录因子的一员，在调控无尾两栖类动物变态发育过程中发挥核心作用。先前对哺乳动物细胞的研究表明，THR通过组蛋白甲基化参与染色质重塑。在本研究中，我们从非洲爪蟾克隆了赖氨酸特异性去甲基化酶基因xLSD1的cDNA，并检测了其与变态发育相关的表达情况。在非洲爪蟾细胞系A6细胞中过表达xLSD1，导致组蛋白H3赖氨酸残基的甲基化状态降低，这表明克隆的xLSD1蛋白具有功能活性。在自然变态发育和甲状腺激素诱导的变态发育过程中，LSD1在mRNA水平的表达在体皮肤和肠道中上调。变态前阶段的幼虫表皮基底细胞和肠上皮细胞被鉴定为表达xLSD1的细胞。在变态高潮阶段，成年表皮基底细胞的祖细胞也表达xLSD1，而成年肠上皮细胞的祖细胞不表达。我们提出，LSD1通过THR或其他转录因子诱导的染色质重塑参与变态发育的调控。
