Novel functional MAR elements of double minute chromosomes in human ovarian cells capable of enhancing gene expression.
Novel functional MAR elements of double minute chromosomes in human ovarian cells capable of enhancing gene expression.
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人类卵巢细胞双微小染色体的新型功能性 MAR 元件能够增强基因表达
DOI：
10.1371/journal.pone.0030419
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Fu S
中科院分区：
文献类型：
--
作者：
Jin Y;Liu Z;Cao W;Ma X;Fan Y;Yu Y;Bai J;Chen F;Rosales J;Lee KY;Fu S
双微体染色体或双微体（DM）是染色体外基因组扩增的细胞遗传学标志，在肿瘤发生中起关键作用。DM中癌基因的扩增拷贝与癌细胞的生长和存活增加有关，但DM中大部分非编码的DNA序列仍有待表征。通过测序和生物信息学分析，我们在人卵巢癌细胞系UACC-1598的682 kb DM中发现了5个新的基质附着区（MARs）。通过电泳迁移率变动分析（EMSA），我们确定了所有5个MAR与核基质在体外的相互作用。此外，qPCR分析显示，这些MAR在体内与核基质相关，表明它们是功能性的。MARs构建体转染人胚肾293T细胞显示出显著增强的基因表达，如通过荧光素酶测定所测量的，这表明所鉴定的MARs，特别是MARs 1至4，在体内调节其靶基因，并且可能参与DM介导的癌基因激活。
Double minute chromosomes or double minutes (DMs) are cytogenetic hallmarks of extrachromosomal genomic amplification and play a critical role in tumorigenesis. Amplified copies of oncogenes in DMs have been associated with increased growth and survival of cancer cells but DNA sequences in DMs which are mostly non-coding remain to be characterized. Following sequencing and bioinformatics analyses, we have found 5 novel matrix attachment regions (MARs) in a 682 kb DM in the human ovarian cancer cell line, UACC-1598. By electrophoretic mobility shift assay (EMSA), we determined that all 5 MARs interact with the nuclear matrix in vitro. Furthermore, qPCR analysis revealed that these MARs associate with the nuclear matrix in vivo, indicating that they are functional. Transfection of MARs constructs into human embryonic kidney 293T cells showed significant enhancement of gene expression as measured by luciferase assay, suggesting that the identified MARS, particularly MARs 1 to 4, regulate their target genes in vivo and are potentially involved in DM-mediated oncogene activation.
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影响因子：
4.8
作者：
Martins, RP;Ostermeier, GC;Krawetz, SA
通讯作者：
Krawetz, SA
影响因子：
6.5
作者：
Lestou, VS;Gascoyne, RD;Horsman, DE
通讯作者：
Horsman, DE
DOI：
10.1073/pnas.130194897
发表时间：
2000-07-05
影响因子：
11.1
作者：
Singer, MJ;Mesner, LD;Hamlin, JL
通讯作者：
Hamlin, JL
影响因子：
5.1
作者：
PEACH, C;VELTEN, J
通讯作者：
VELTEN, J
DOI：
10.1007/bf02717000
发表时间：
2005-12-01
期刊：
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
影响因子：
--
作者：
Gebhart, Erich
通讯作者：
Gebhart, Erich