Identification of HiNF-P, a Key Activator of Cell Cycle-Controlled Histone H4 Genes at the Onset of S Phase
| Autor: | J. Wade Harper, Andre J. Van Wijnen, Hayk Hovhannisyan, S. Kaleem Zaidi, Gary S. Stein, Yue Wei, Rong Lin Xie, Ricardo F. Medina, Janet L. Stein, Partha Mitra |
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| Rok vydání: | 2003 |
| Předmět: |
DNA
Complementary Molecular Sequence Data Biology S Phase Histones Histone H4 Histone H1 Histone methylation Histone H2A Humans Histone code Amino Acid Sequence Cloning Molecular Molecular Biology Transcriptional Regulation Base Sequence Cyclin-dependent kinase 3 Zinc Fingers Cell Biology Molecular biology Recombinant Proteins Molecular Weight Repressor Proteins Gene Expression Regulation Histone methyltransferase Chromatin immunoprecipitation HeLa Cells Signal Transduction Transcription Factors |
| Zdroj: | Molecular and Cellular Biology. 23:8110-8123 |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/mcb.23.22.8110-8123.2003 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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