Transcriptional activation of the histone nuclear factor P (HiNF-P) gene by HiNF-P and its cyclin E/CDK2 responsive co-factor p220NPAT defines a novel autoregulatory loop at the G1/S phase transition
Department of Cell Biology and Cancer Center
Animals; Cyclin E; Cyclin-Dependent Kinase 2; *G1 Phase; Hela Cells; Homeostasis; Humans; Mice; Models, Biological; Models, Genetic; NIH 3T3 Cells; Promoter Regions (Genetics); Regulatory Elements, Transcriptional; Repressor Proteins; *S Phase; Signal Transduction; *Trans-Activation (Genetics); Transcription Factors
Life Sciences | Medicine and Health Sciences
Histone nuclear factor P (HiNF-P) activates histone H4 gene transcription at the G1/S phase transition upon association with its cyclin E/CDK2 responsive co-factor p220NPAT. Here we characterize the gene regulatory pathways that control the proliferation-related expression of HiNF-P. The HiNF-P locus contains a single TATA-less 0.6 kbp promoter with multiple phylogenetically conserved transcription factor recognition motifs. Transient reporter gene assays with HiNF-P promoter deletions show that there are at least three distinct activating regions (-387/-201, -201/-100 and -100/-1) that support maximal transcription. HiNF-P gene transcription is activated by SP1 through the -100/-1 domain and repressed by E2F1 through the -201/-100 domain. The multifunctional co-regulators CBP and p300 also stimulate HiNF-P gene transcription through the -201/-1 core promoter. Importantly, the HiNF-P promoter is activated by both HiNF-P and p220NPAT. This autoregulatory activation is further enhanced by cyclin E and CDK2, while blocked by CDK inhibition (i.e., p57KIP2 p27KIP1, p21CIP). Thus, the HiNF-P gene is a key non-histone target of p220NPAT and HiNF-P. The dependence of HiNF-P gene transcription on cyclin E/CDK2/p220NPAT signaling defines a novel feed-forward loop that may sustain HiNF-P expression in proliferating cells to support the cell cycle regulated synthesis of histone H4 proteins.
DOI of Published Version
Gene. 2007 Nov 1;402(1-2):94-102. Epub 2007 Aug 9. Link to article on publisher's site
Xie R, Liu L, Mitra P, Stein JL, Van Wijnen AJ, Stein GS. (2007). Transcriptional activation of the histone nuclear factor P (HiNF-P) gene by HiNF-P and its cyclin E/CDK2 responsive co-factor p220NPAT defines a novel autoregulatory loop at the G1/S phase transition. Open Access Publications by UMMS Authors. https://doi.org/10.1016/j.gene.2007.07.027. Retrieved from https://escholarship.umassmed.edu/oapubs/1258