Novel Functional MAR Elements of Double Minute Chromosomes in Human Ovarian Cells Capable of Enhancing Gene ExpressionReport as inadecuate




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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.



Author: Yan Jin , Zheng Liu , Wei Cao, Xinying Ma, Yihui Fan, Yang Yu, Jing Bai, Feng Chen, Jesusa Rosales, Ki-Young Lee, Songbin Fu

Source: http://plos.srce.hr/



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