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PMID:17974976

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Citation

Medina, R, van der Deen, M, Miele-Chamberland, A, Xie, RL, van Wijnen, AJ, Stein, JL and Stein, GS (2007) The HiNF-P/p220NPAT cell cycle signaling pathway controls nonhistone target genes. Cancer Res. 67:10334-42

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.

Links

PubMed Online version:10.1158/0008-5472.CAN-07-1560

Keywords

Binding Sites; Carrier Proteins/genetics; Cell Cycle; Cell Cycle Proteins/genetics; Cell Cycle Proteins/physiology; Cell Line, Tumor; DNA Damage; DNA-Activated Protein Kinase/genetics; DNA-Binding Proteins/genetics; Gene Expression Regulation; Genes, Regulator; Humans; Nuclear Proteins/genetics; Nuclear Proteins/physiology; Protein Kinases/genetics; Protein-Serine-Threonine Kinases/genetics; Repressor Proteins/physiology; Signal Transduction/physiology; Tumor Suppressor Proteins/genetics

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:NPAT

enables

GO:0003713: transcription coactivator activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:HINFP

involved_in

GO:0006281: DNA repair

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:HINFP

involved_in

GO:0000077: DNA damage checkpoint

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:HINFP

involved_in

GO:0045893: positive regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:HINFP

enables

GO:0000976: transcription regulatory region sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:HINFP

involved_in

GO:0010629: negative regulation of gene expression

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:HINFP

involved_in

GO:0010628: positive regulation of gene expression

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:H2AX

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:H2AX

involved_in

GO:0000077: DNA damage checkpoint

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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