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首页> 外文期刊>Journal of Cellular Physiology >Cell type specific chromosome territory organization in the interphase nucleus of normal and cancer cells.
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Cell type specific chromosome territory organization in the interphase nucleus of normal and cancer cells.

机译：细胞类型特定的染色体区域间期核的组织正常和癌症细胞。

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Numerous studies indicate that the genome of higher eukaryotes is organized into distinct chromosome territories and that the 3-D arrangement of these territories may be closely connected to genomic function and the global regulation of gene expression. Despite this progress, the degree of non-random arrangement remains unclear and no overall model has been proposed for chromosome territory associations. To address this issue, a re-FISH approach was combined with computational analysis to analysis the pair-wise associations for six pairs of human chromosomes (chr #1, 4, 11, 12, 16, 18) in the G(0) state of normal human WI38 lung fibroblast and MCF10A epithelial breast cells. Similar levels of associations were found in WI38 and MCF10A for several of the chromosomes whereas others showed striking differences. A novel computational geometric approach, the generalized median graph (GMG), revealed a preferred probabilistic arrangement distinct for each cell line. Statistical analysis demonstrated that approximately 50% of the associations depicted in the GMG models are present in each individual nucleus. A nearly twofold increase of chromosome 4/16 associations in a malignant breast cancer cell line (MCFCA1a) compared to the related normal epithelial cell line (MCF10A) further demonstrates cancer related changes in chromosome arrangements. Our findings of highly preferred chromosome association profiles that are cell type specific and undergo alterations in cancer cells, lead us to propose a probabilistic chromosome code whereby the 3-D association profile of chromosomes contributes to the functional landscape of the cell nucleus, the global regulation of gene expression and the epigenetic state of chromatin.
机译：大量研究表明的基因组高等真核生物组织成不同的染色体的领土,3 d安排这些领土可能密切连接到基因功能和全球调节基因的表达。进步的程度的非随机安排还不清楚,没有整体模型提出了染色体区域关联。为了解决这个问题,一个是re-FISH方法结合计算分析来分析六对的双向关联人染色体(空空的# 1,4,11、12、16、18)G(0)的状态正常的人类WI38肺纤维母细胞和MCF10A乳房上皮细胞。协会在WI38被发现和水平染色体而MCF10A数他人表现出显著的不同。计算几何的方法,广义中位数图(GMG),显示优先概率安排不同的每一个细胞线。大约50%的关联中描述GMG模型存在于每一个个人原子核。4/16联系在一个恶性乳腺癌细胞系(MCFCA1a)比较相关正常上皮细胞系MCF10A进一步表明癌症相关的染色体的变化安排。细胞的染色体关联概要文件具体类型和接受改变癌症细胞,让我们提出一个概率染色体编码,3 d协会的染色体导致的细胞核的功能景观,全球基因表达和调控染色质的表观遗传状态。

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