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Cell, Tumor, and Stem Cell Biology |
Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts
Requests for reprints: Gary S. Stein, Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655. Phone: 508-856-5625; Fax: 508-856-6800; E-mail: Gary.Stein{at}umassmed.edu.
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. [Cancer Res 2007;67(21):10334–42]
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R. Xie, R. Medina, Y. Zhang, S. Hussain, J. Colby, P. Ghule, S. Sundararajan, M. Keeler, L.-J. Liu, M. van der Deen, et al. The histone gene activator HINFP is a nonredundant cyclin E/CDK2 effector during early embryonic cell cycles PNAS, July 28, 2009; 106(30): 12359 - 12364. [Abstract] [Full Text] [PDF] |
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P. N. Ghule, Z. Dominski, X.-c. Yang, W. F. Marzluff, K. A. Becker, J. W. Harper, J. B. Lian, J. L. Stein, A. J. van Wijnen, and G. S. Stein Staged assembly of histone gene expression machinery at subnuclear foci in the abbreviated cell cycle of human embryonic stem cells PNAS, November 4, 2008; 105(44): 16964 - 16969. [Abstract] [Full Text] [PDF] |
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