Identification of a predominant co-regulation among kinetochore genes, prospective regulatory elements, and association with genomic instability

William C. Reinhold, Indri Erliandri, Hongfang D Liu, Gabriele Zoppoli, Yves Pommier, Vladimir Larionov

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 genes, including the transcription factors CREB1, E2F1, FOXE1, and FOXM1, DNA copy number variation, and microRNAs has-miR-200a, 23a, 23b, 30a, 30c, 27b, 374b, 365. Thus, our results provide a template for experimental studies on the regulation of genes encoding kinetochore proteins, the process that, when aberrant, leads to the aneuploidy that is a hallmark of many cancers. We propose that the comparison of expression profiles in the NCI-60 cell line panel could be a tool for the identification of other gene groups whose products are involved in the assembly of organelle protein complexes.

Original languageEnglish (US)
Article numbere25991
JournalPLoS One
Volume6
Issue number10
DOIs
StatePublished - Oct 10 2011

Fingerprint

Kinetochores
kinetochores
Genomic Instability
Regulator Genes
Genes
Association reactions
genomics
DNA Copy Number Variations
Gene encoding
genes
Cells
E2F1 Transcription Factor
DNA
Cell Line
Transcription
cell lines
Microarrays
Chromosomes
Chromosome Segregation
MicroRNAs

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Identification of a predominant co-regulation among kinetochore genes, prospective regulatory elements, and association with genomic instability. / Reinhold, William C.; Erliandri, Indri; Liu, Hongfang D; Zoppoli, Gabriele; Pommier, Yves; Larionov, Vladimir.

In: PLoS One, Vol. 6, No. 10, e25991, 10.10.2011.

Research output: Contribution to journalArticle

Reinhold, William C. ; Erliandri, Indri ; Liu, Hongfang D ; Zoppoli, Gabriele ; Pommier, Yves ; Larionov, Vladimir. / Identification of a predominant co-regulation among kinetochore genes, prospective regulatory elements, and association with genomic instability. In: PLoS One. 2011 ; Vol. 6, No. 10.
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