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.
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.
Xie
Rong-Lin
RL
Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Liu
Lijun
L
Mitra
Partha
P
Stein
Janet L
JL
van Wijnen
Andre J
AJ
Stein
Gary S
GS
D000818:Animals; D019927:Cyclin E / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism*; D016193:G1 Phase; D006367:HeLa Cells; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D051379:Mice; D008954:Models, Biological; D008957:Models, Genetic; D041681:NIH 3T3 Cells; D011401:Promoter Regions, Genetic; D050436:Regulatory Elements, Transcriptional; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D016196:S Phase; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D015533:Transcriptional Activation