Activation of a cell-cycle-regulated histone gene by the oncogenic transcription factor IRF-2

Nature. 1995 Sep 28;377(6547):362-5. doi: 10.1038/377362a0.


The human histone H4 gene FO108 is regulated during the cell cycle with a peak in transcription during early S phase. The cell-cycle element (CCE) required for H4 histone activation is a sequence of 11 base pairs that binds a protein factor in electrophoretic mobility shift assays that has been designated histone nuclear factor M (HiNF-M). Here we report the purification of HiNF-M, and show it to be a protein of relative molecular mass (M(r)) 48K that is identical to interferon (IFN) regulatory factor 2 (IRF-2), a negative transcriptional regulator of the IFN response. Recombinant IRF-2 (as well as the related protein IRF-1 (ref. 5)) binds the CCE specifically and activates transcription of this H4 histone gene. IRF-2 has been shown to have oncogenic potential, and our results demonstrate a link between IRF-2 and a gene that is functionally coupled to DNA replication and cell-cycle progression at the G1/S phase transition.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Cycle / physiology*
  • Cell Line
  • Cricetinae
  • DNA
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation*
  • Haplorhini
  • HeLa Cells
  • Histones / genetics*
  • Humans
  • Interferon Regulatory Factor-1
  • Interferon Regulatory Factor-2
  • Molecular Sequence Data
  • Phosphoproteins / metabolism
  • Repressor Proteins*
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Transfection


  • DNA-Binding Proteins
  • Histones
  • IRF1 protein, human
  • IRF2 protein, human
  • Interferon Regulatory Factor-1
  • Interferon Regulatory Factor-2
  • Phosphoproteins
  • Repressor Proteins
  • Transcription Factors
  • DNA