The HiNF-P/p220NPAT cell cycle signaling pathway controls nonhistone target genes
Department of Cell Biology
Medical Subject Headings
Binding Sites; Carrier Proteins; *Cell Cycle; Cell Cycle Proteins; Cell Line, Tumor; DNA Damage; DNA-Activated Protein Kinase; DNA-Binding Proteins; *Gene Expression Regulation; Genes, Regulator; Humans; Nuclear Proteins; Protein Kinases; Protein-Serine-Threonine Kinases; Repressor Proteins; Signal Transduction; Tumor Suppressor Proteins
HiNF-P and its cofactor p220(NPAT) are principal factors regulating histone gene expression at the G(1)-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.
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Citation: Cancer Res. 2007 Nov 1;67(21):10334-42. Link to article on publisher's site
Medina, Ricardo F.; Van der Deen, Margaretha; Miele, Angela; Xie, Ronglin; Van Wijnen, Andre J.; Stein, Janet L.; and Stein, Gary S., "The HiNF-P/p220NPAT cell cycle signaling pathway controls nonhistone target genes" (2007). Stein, Stein, Lian, vanWijnen Lab Publications. 49.