Chromatin interaction analysis reveals changes in small chromosome and telomere clustering between epithelial and breast cancer cells.
Chromatin interaction analysis reveals changes in small chromosome and telomere clustering between epithelial and breast cancer cells.
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DOI：
10.1186/s13059-015-0768-0
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发表时间：
2015-09-28
期刊：
影响因子：
12.3
通讯作者：
Stein GS
中科院分区：
文献类型：
--
作者：
Barutcu AR;Lajoie BR;McCord RP;Tye CE;Hong D;Messier TL;Browne G;van Wijnen AJ;Lian JB;Stein JL;Dekker J;Imbalzano AN;Stein GS
在癌症和其他病理状态下，高阶染色质结构经常受到干扰。虽然已经在正常组织和乳腺癌组织之间绘制了几个遗传和表观遗传差异的图表，但在肿瘤发生过程中高阶染色质组织的变化还没有得到充分的研究。为了探讨乳腺上皮细胞和乳腺癌细胞高阶染色质结构的差异，我们对MCF-10A乳腺癌细胞和MCF-7乳腺癌细胞进行了Hi-C分析。我们的研究表明，与MCF-10A上皮细胞中染色体间的相互作用频率相比，MCF-7乳腺癌基因组中富含基因的小染色体chr16至chr22彼此之间的相互作用频率降低。有趣的是，这一发现与MCF-7细胞中chr16-22上开放间隔的发生率较高有关。对位于chr16-22上改变的间隔区的MCF-7上调基因的通路分析揭示了与WNT信号抑制相关的通路。不同细胞系之间的染色体内相互作用也存在差异；MCF-10A细胞中的端粒和亚端粒区域比MCF-7细胞中观察到的更频繁的相互作用。我们展示了上皮性癌细胞和乳腺癌细胞之间染色体组织和基因表达之间复杂关系的证据。重要的是，这项工作提供了高阶染色质动力学的全基因组视角，并为研究两个通常用于研究乳腺癌进展的细胞系中的高阶染色质相互作用提供了资源。本文的在线版本(doi：10.1186/s13059-0150768-0)包含补充材料，授权用户可以使用。
Higher-order chromatin structure is often perturbed in cancer and other pathological states. Although several genetic and epigenetic differences have been charted between normal and breast cancer tissues, changes in higher-order chromatin organization during tumorigenesis have not been fully explored. To probe the differences in higher-order chromatin structure between mammary epithelial and breast cancer cells, we performed Hi-C analysis on MCF-10A mammary epithelial and MCF-7 breast cancer cell lines. Our studies reveal that the small, gene-rich chromosomes chr16 through chr22 in the MCF-7 breast cancer genome display decreased interaction frequency with each other compared to the inter-chromosomal interaction frequency in the MCF-10A epithelial cells. Interestingly, this finding is associated with a higher occurrence of open compartments on chr16–22 in MCF-7 cells. Pathway analysis of the MCF-7 up-regulated genes located in altered compartment regions on chr16–22 reveals pathways related to repression of WNT signaling. There are also differences in intra-chromosomal interactions between the cell lines; telomeric and sub-telomeric regions in the MCF-10A cells display more frequent interactions than are observed in the MCF-7 cells. We show evidence of an intricate relationship between chromosomal organization and gene expression between epithelial and breast cancer cells. Importantly, this work provides a genome-wide view of higher-order chromatin dynamics and a resource for studying higher-order chromatin interactions in two cell lines commonly used to study the progression of breast cancer. The online version of this article (doi:10.1186/s13059-015-0768-0) contains supplementary material, which is available to authorized users.