Oikawa Kosuke, Yoshida Keiichi, Takanashi Masakatsu, Tanabe Hideyuki, Kiyuna Tomoharu, Ogura Maki, Saito Akira, Umezawa Akihiro, Kuroda Masahiko
Department of Pathology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan.
Biochem Biophys Res Commun. 2008 Sep 19;374(2):361-4. doi: 10.1016/j.bbrc.2008.07.044. Epub 2008 Jul 18.
Each chromosome occupies its own-specific space called a 'territory' within the interphase nucleus, and the arrangement of chromosome territories (CTs) is important in epigenetic mechanisms. The molecular mechanism to determine the positioning of CTs, however, remains unknown. On the other hand, dioxin is known to be the typical environmental pollutant that affects a wide variety of biological events in many species. Here, we show that dioxin enlarges the minimum distance between chromosome 12 and chromosome 16 territories in human preadipocyte cells, and the alteration of chromosome positioning is canceled by an aryl hydrocarbon receptor (AhR) antagonist alpha-naphthoflavone. Thus, AhR may be a key molecule to regulate chromosome positioning. Our results suggest a novel effect of dioxin toxicity, and demonstrate a clue to reveal the novel molecular mechanism for the arrangement of CTs.
在间期细胞核内,每条染色体都占据其自身特定的空间,称为“区域”,染色体区域(CTs)的排列在表观遗传机制中很重要。然而,决定CTs定位的分子机制仍然未知。另一方面,已知二噁英是一种典型的环境污染物,会影响许多物种的多种生物事件。在这里,我们表明二噁英会扩大人类前脂肪细胞中12号染色体和16号染色体区域之间的最小距离,并且芳烃受体(AhR)拮抗剂α-萘黄酮可消除染色体定位的改变。因此,AhR可能是调节染色体定位的关键分子。我们的结果表明了二噁英毒性的一种新作用,并为揭示CTs排列的新分子机制提供了线索。