identification of a predominant co-regulation among kinetochore genes, prospective regulatory elements, and association with genomic instability着丝粒之间的识别主要co-regulation基因,准监管元素,与基因组不稳定性.pdfVIP

Identification of a Predominant Co-Regulation among Kinetochore Genes, Prospective Regulatory Elements, and Association with Genomic Instability 1 1 1,2 1,3 1 William C. Reinhold *, Indri Erliandri , Hongfang Liu , Gabriele Zoppoli , Yves Pommier , Vladimir Larionov1* 1 Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America, 2 Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, United States of America, 3 Department of Internal Medicine, University of Genova, Genova, Italy Abstract The NCI-60 cell line panel is the most extensively characterized set of cells in existence, and has been used extensively as a screening tool for drug discovery. Previously, the potential of this panel has not been applied to the fundamental cellular processes of chromosome segregation. In the current study, we used data from multiple microarray platforms accumulated for the NCI-60 to characterize an expression pattern of genes involved in kinetochore assembly. This analysis revealed that 17 genes encoding the constitutive centromere associated network of the kinetochore core (the CCAN complex) plus four additional genes with established importance in kinetochore maintenance (CENPE, CENPF, INCENP, and MIS12) exhibit similar patterns of expression in the NCI-60, suggesting a mechanism for co-regulated transcription of these genes which is maintained despite the multiple genetic and epigenetic rearrangements accumulated in these cells (such as variations in DNA copy number and karyotypic complexity). A complex group of potential regulatory influences are identified for these