Kuroda Masahiko, Tanabe Hideyuki, Yoshida Keiichi, Oikawa Kosuke, Saito Akira, Kiyuna Tomoharu, Mizusawa Hiroshi, Mukai Kiyoshi
Department of Pathology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan.
J Cell Sci. 2004 Nov 15;117(Pt 24):5897-903. doi: 10.1242/jcs.01508.
Chromosomes are highly restricted to specific chromosome territories within the interphase nucleus. The arrangement of chromosome territories is non-random, exhibiting a defined radial distribution as well as a preferential association with specific nuclear compartments, which indicates a functional role for chromosome-territory organization in the regulation of gene expression. In this report, we focus on changes in adipocyte differentiation that are related to a specific chromosomal translocation associated with liposarcoma tumorigenesis, t(12;16). We have examined the relative and radial positioning of the chromosome territories of human chromosomes 12 and 16 during adipocyte differentiation, and detected a close association between the territories of chromosomes 12 and 16 in differentiated adipocytes, an association not observed in preadipocytes. Although further studies are required to elucidate the underlying reasons for the adipocyte-specific translocation of chromosomes 12 and 16, our observations indicate that alteration of relative chromosome positioning might play a key role in the tumorigenesis of human liposarcomas. In addition, these results demonstrate the potential impact of higher order chromatin organization on the epigenetic mechanisms that control gene expression and gene silencing during cell differentiation.
染色体在间期核内高度局限于特定的染色体区域。染色体区域的排列是非随机的，呈现出明确的径向分布以及与特定核区室的优先关联，这表明染色体区域组织在基因表达调控中具有功能作用。在本报告中，我们聚焦于与脂肪肉瘤肿瘤发生相关的特定染色体易位t(12;16)所涉及的脂肪细胞分化变化。我们研究了人类12号和16号染色体的染色体区域在脂肪细胞分化过程中的相对位置和径向定位，发现在分化的脂肪细胞中12号和16号染色体区域紧密关联，而在前脂肪细胞中未观察到这种关联。尽管需要进一步研究来阐明12号和16号染色体在脂肪细胞中特异性易位的潜在原因，但我们的观察结果表明相对染色体定位的改变可能在人类脂肪肉瘤的肿瘤发生中起关键作用。此外，这些结果证明了高阶染色质组织对细胞分化过程中控制基因表达和基因沉默的表观遗传机制的潜在影响。
