Title

The HiNF-P/p220NPAT cell cycle signaling pathway controls nonhistone target genes

UMMS Affiliation

Department of Cell Biology

Date

11-3-2007

Document Type

Article

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

Disciplines

Cell Biology

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.

Rights and Permissions

Citation: Cancer Res. 2007 Nov 1;67(21):10334-42. Link to article on publisher's site

Related Resources

Link to Article in PubMed

PubMed ID

17974976