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

THE human histone H4 gene FO108 is regulated during the cell cycle with a peak in transcription during early S phase^{1, 2}. The cell-cycle element (CCE) required for H4 histone activation is a sequence of 11 base pairs that binds a protein factor in electrophor-etic mobility shift assays that has been designated histone nuclear factor M (HiNF-M)^{2, 3}. 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 response⁴. 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 potential⁶, 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 Gl/S phase transition.