Identification of primary transcriptional regulation of cell cycle-regulated genes upon DNA damage.
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.
Zhou
Tong
T
Department of Pathology and Laboratory Medicine, Center for Environmental Health and Susceptibility, and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Chou
Jeff
J
Mullen
Thomas E
TE
Elkon
Rani
R
Zhou
Yingchun
Y
Simpson
Dennis A
DA
Bushel
Pierre R
PR
Paules
Richard S
RS
Lobenhofer
Edward K
EK
Hurban
Patrick
P
Kaufmann
William K
WK
D002453:Cell Cycle / Q000235:genetics* / Q000528:radiation effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis / Q000528:radiation effects; D004249:DNA Damage / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D019098:Telomerase / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics*; D014162:Transfection
D004247:DNA; C509186:TERT protein, human; D019098:Telomerase