Alteration of chromosome positioning during adipocyte differentiation

Author:

Kuroda Masahiko123,Tanabe Hideyuki4,Yoshida Keiichi13,Oikawa Kosuke123,Saito Akira5,Kiyuna Tomoharu6,Mizusawa Hiroshi7,Mukai Kiyoshi1

Affiliation:

1. Department of Pathology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan

2. CREST Research Project, Japan Science and Technology Corporation, 4-1-6 Kawaguchi, Saitama, 332-0012, Japan

3. Shinanomachi Research Park, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

4. Department of Biosystems Science, School of Advanced Sciences, The Graduate University for Advanced Studies (Sokendai), Shonan Village, Hayama, Kanagawa 240-0193, Japan

5. Bioinformatics Business Promotion Department, NEC Corporation, 7-1 Shiba 5-chome, Minato-ku, Tokyo 108-8001, Japan

6. Fundamental and Environmental Research Laboratories, NEC Corporation, 34 Miyukigaoka, Tsukuba, Ibaraki 305-8501, Japan

7. Cell bank laboratory, Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan

Abstract

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.

Publisher

The Company of Biologists

Subject

Cell Biology

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