TY - JOUR
T1 - The HiNF-P/p220NPAT cell cycle signaling pathway controls nonhistone target genes
AU - Medina, Ricardo
AU - Van Der Deen, Margaretha
AU - Miele-Chamberland, Angela
AU - Xie, Rong Lin
AU - Van Wijnen, Andre J.
AU - Stein, Janet L.
AU - Stein, Gary S.
PY - 2007/11/1
Y1 - 2007/11/1
N2 - HiNF-P and its cofactor p220NPAT are principal factors regulating histone gene expression at the G1-S phase cell cycle transition. Here, we have investigated whether HiNF-P controls other cell cycle- and cancer-related genes. We used cDNA microarrays to monitor responsiveness of gene expression to small interfering RNA-mediated depletion of HiNF-P. Candidate HiNF-P target genes were examined for the presence of HiNF-P recognition motifs, in vitro HiNF-P binding to DNA,and in vivo association by chromatin immunoprecipitations and functional reporter gene assays. Of 177 proliferation-related genes we tested, 20 are modulated in HiNF-P-depleted cells and contain putative HiNF-P binding motifs. We validated that at least three genes (i.e., ATM, PRKDC, and CKS2) are HiNF-P dependent and provide data indicating that the DNA damage response is altered in HiNF-P -depleted cells. We conclude that,in addition to histone genes, HiNF-P also regulates expression of nonhistone targets that influence competency for cell cycle progression.
AB - HiNF-P and its cofactor p220NPAT are principal factors regulating histone gene expression at the G1-S phase cell cycle transition. Here, we have investigated whether HiNF-P controls other cell cycle- and cancer-related genes. We used cDNA microarrays to monitor responsiveness of gene expression to small interfering RNA-mediated depletion of HiNF-P. Candidate HiNF-P target genes were examined for the presence of HiNF-P recognition motifs, in vitro HiNF-P binding to DNA,and in vivo association by chromatin immunoprecipitations and functional reporter gene assays. Of 177 proliferation-related genes we tested, 20 are modulated in HiNF-P-depleted cells and contain putative HiNF-P binding motifs. We validated that at least three genes (i.e., ATM, PRKDC, and CKS2) are HiNF-P dependent and provide data indicating that the DNA damage response is altered in HiNF-P -depleted cells. We conclude that,in addition to histone genes, HiNF-P also regulates expression of nonhistone targets that influence competency for cell cycle progression.
UR - http://www.scopus.com/inward/record.url?scp=35949003532&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=35949003532&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-07-1560
DO - 10.1158/0008-5472.CAN-07-1560
M3 - Article
C2 - 17974976
AN - SCOPUS:35949003532
SN - 0008-5472
VL - 67
SP - 10334
EP - 10342
JO - Cancer research
JF - Cancer research
IS - 21
ER -