GSBS Student Publications
Title
Identification of HiNF-P, a key activator of cell cycle-controlled histone H4 genes at the onset of S phase
Publication Date
2003-10-31
UMMS Affiliation
Graduate School of Biomedical Sciences; Department of Cell Biology and Cancer Center
Document Type
Article
Disciplines
Life Sciences | Medicine and Health Sciences
Abstract
At the G(1)/S phase cell cycle transition, multiple histone genes are expressed to ensure that newly synthesized DNA is immediately packaged as chromatin. Here we have purified and functionally characterized the critical transcription factor HiNF-P, which is required for E2F-independent activation of the histone H4 multigene family. Using chromatin immunoprecipitation analysis and ligation-mediated PCR-assisted genomic sequencing, we show that HiNF-P interacts with conserved H4 cell cycle regulatory sequences in vivo. Antisense inhibition of HiNF-P reduces endogenous histone H4 gene expression. Furthermore, we find that HiNF-P utilizes NPAT/p220, a substrate of the cyclin E/cyclin-dependent kinase 2 (CDK2) kinase complex, as a key coactivator to enhance histone H4 gene transcription. The biological role of HiNF-P is reflected by impeded cell cycle progression into S phase upon antisense-mediated reduction of HiNF-P levels. Our results establish that HiNF-P is the ultimate link in a linear signaling pathway that is initiated with the growth factor-dependent induction of cyclin E/CDK2 kinase activity at the restriction point and culminates in the activation of histone H4 genes through HiNF-P at the G(1)/S phase transition.
Source
Mol Cell Biol. 2003 Nov;23(22):8110-23.
Journal/Book/Conference Title
Molecular and cellular biology
Related Resources
PubMed ID
14585971
Repository Citation
Mitra, Partha; Xie, Ronglin; Medina, Ricardo F.; Hovhannisyan, Hayk; Zaidi, Sayyed K.; Wei, Yue; Harper, J. Wade; Stein, Janet L.; Van Wijnen, Andre J.; and Stein, Gary S., "Identification of HiNF-P, a key activator of cell cycle-controlled histone H4 genes at the onset of S phase" (2003). GSBS Student Publications. 874.
https://escholarship.umassmed.edu/gsbs_sp/874