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Identification of Primary Transcriptional Regulation of Cell Cycle-Regulated Genes upon DNA Damage
Tong Zhou, Jeff Chou, Thomas E. Mullen, Rani Elkon, Yingchun Zhou, Dennis A. Simpson, Pierre R. Bushel, Richard S. Paules, Edward K. Lobenhofer, Patrick Hurban and William K. Kaufmann
volume 6 | issue 8
15 April 2007Pages: 972 - 981
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The changes in global gene expression in response to DNA damage may derive from either direct induction or repression by transcriptional regulation or indirectly by synchronization of cells to specific cell cycle phases, such as G1 or G2. We developed a model that successfully estimated the expression levels of >400 cell-cycle-regulated genes in normal human fibroblasts based on the proportions of cells in each phase of the cell cycle. By isolating effects on the gene expression associated with the cell cycle phase redistribution after genotoxin treatment, the direct transcriptional target genes were distinguished from genes for which expression changed secondary to cell synchronization. Application of this model to ionizing radiation (IR)-treated normal human fibroblasts identified 150 of 406 cycle-regulated genes as putative direct transcriptional targets of IR-induced DNA damage. Changes in expression of these genes after IR treatment derived from both direct transcriptional regulation and cell cycle synchronization.
Authors
Tong Zhou
University of North Carolina, Chapel Hill, North Carolina
Jeff Chou
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina
Thomas E. Mullen
University of North Carolina, Chapel Hill, North Carolina
Rani Elkon
Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Yingchun Zhou
University of North Carolina, Chapel Hill, North Carolina
Dennis A. Simpson
University of North Carolina, Chapel Hill, North Carolina
Pierre R. Bushel
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina
Richard S. Paules
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina
Edward K. Lobenhofer
Cogenics, Morrisville, North Carolina
Patrick Hurban
Cogenics, Morrisville, North Carolina
William K. Kaufmann
University of North Carolina School of Medicine
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.