The interactome of the histone gene regulatory factor HiNF-P suggests novel cell cycle related roles in transcriptional control and RNA processing
Biochemistry & Molecular Pharmacology
Graduate School of Biomedical Sciences; Department of Cell Biology
Medical Subject Headings
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
Life Sciences | Medicine and Health Sciences
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.
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Citation: J Cell Biochem. 2007 Sep 1;102(1):136-48. Link to article on publisher's site
Miele, Angela; Medina, Ricardo F.; Van Wijnen, Andre J.; Stein, Gary S.; and Stein, Janet L., "The interactome of the histone gene regulatory factor HiNF-P suggests novel cell cycle related roles in transcriptional control and RNA processing" (2007). GSBS Student Publications. 436.