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

Angela Miele, Ricardo Medina, Andre J. Van Wijnen, Gary S. Stein, Janet L. Stein

Research output: Contribution to journalArticle

15 Scopus citations

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 p220NPAT 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.

Original languageEnglish (US)
Pages (from-to)136-148
Number of pages13
JournalJournal of cellular biochemistry
Volume102
Issue number1
DOIs
StatePublished - Sep 1 2007

Keywords

  • CDK2
  • Cajal body
  • Cell cycle
  • Cyclin
  • Histone
  • RNA processing
  • Transcription
  • Zn finger

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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