The interactome of the histone gene regulatory factor HiNF-P suggests novel cell cycle related roles in transcriptional control and RNA processing.
HiNF-P is a recently identified histone H4 subtype specific transcriptional regulator that associates with the conserved cell cycle control element in the proximal promoter regions of histone H4 genes. HiNF-P interacts with the global histone gene regulator and direct cyclin E/CDK2 substrate p220(NPAT) to potently upregulate histone H4 gene transcription ... at the G1/S phase transition in response to cyclin E/CDK2 signaling. To gain insight into the function of HiNF-P in a broader cellular context, we performed a yeast two-hybrid screen to identify its novel interacting proteins. In this study, we detected 67 candidate HiNF-P interacting proteins of varying cellular functions. We have identified multiple RNA associated proteins, including the splicing co-factor SRm300. HiNF-P and SRm300 interact in yeast two-hybrid, co-immunoprecipitation, and co-immunofluorescence assays. Our screen also identified several gene regulators that associate with HiNF-P including THAP7. HiNF-P and THAP7 interact in mammalian cells and THAP7 abrogates HiNF-P/p220 mediated activation of histone H4 gene transcription, consistent with its known role as a transcriptional repressor. Finally, we identified several proliferation related proteins including Ki-67 and X transactivated protein 2 (XTP2) which may be functioning with HiNF-P in cell cycle regulation. The HiNF-P interactome indicates that HiNF-P is a multifunctional gene regulator with a large functional network and roles beyond cell cycle-dependent histone gene regulation.
Mesh Terms:
Cell Cycle, Cell Line, Tumor, Cell Proliferation, Chromosomal Proteins, Non-Histone, Gene Expression Regulation, Humans, Ki-67 Antigen, RNA Processing, Post-Transcriptional, RNA-Binding Proteins, Repressor Proteins, Transcription, Genetic, Two-Hybrid System Techniques
Cell Cycle, Cell Line, Tumor, Cell Proliferation, Chromosomal Proteins, Non-Histone, Gene Expression Regulation, Humans, Ki-67 Antigen, RNA Processing, Post-Transcriptional, RNA-Binding Proteins, Repressor Proteins, Transcription, Genetic, Two-Hybrid System Techniques
J. Cell. Biochem.
Date: Sep. 01, 2007
PubMed ID: 17577209
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