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The interactome of the histone gene regulatory factor HiNF‐P suggests novel cell cycle related roles in transcriptional control and RNA processing

2007; Wiley; Volume: 102; Issue: 1 Linguagem: Inglês

10.1002/jcb.21284

1097-4644

Angela Miele, Ricardo Medina, André J. van Wijnen, Gary S. Stein, Janet L. Stein,

Protein Degradation and Inhibitors

Abstract 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. J. Cell. Biochem. 102: 136–148, 2007. © 2007 Wiley‐Liss, Inc.