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

Ricardo Medina, Margaretha Van Der Deen, Angela Miele-Chamberland, Rong Lin Xie, Andre J van Wijnen, Janet L. Stein, Gary S. Stein

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16 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)10334-10342
Number of pages9
JournalCancer Research
Volume67
Issue number21
DOIs
StatePublished - Nov 1 2007
Externally publishedYes

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Medina, R., Van Der Deen, M., Miele-Chamberland, A., Xie, R. L., van Wijnen, A. J., Stein, J. L., & Stein, G. S. (2007). The HiNF-P/p220NPAT cell cycle signaling pathway controls nonhistone target genes. Cancer Research, 67(21), 10334-10342. https://doi.org/10.1158/0008-5472.CAN-07-1560