The HiNF-P/p220NPAT cell cycle signaling pathway controls nonhistone target genes.
Cancer Res
; 67(21): 10334-42, 2007 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-17974976
ABSTRACT
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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Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
/
Proteínas Nucleares
/
Transdução de Sinais
/
Ciclo Celular
/
Regulação da Expressão Gênica
/
Proteínas de Ciclo Celular
Limite:
Humans
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article