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. 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.
Vaughan
P S
PS
Department of Cell Biology, University of Massachusetts Medical Center, Worcester 01655, USA.
Aziz
F
F
van Wijnen
A J
AJ
Wu
S
S
Harada
H
H
Taniguchi
T
T
Soprano
K J
KJ
Stein
J L
JL
Stein
G S
GS
D000818:Animals; D001483:Base Sequence; D002453:Cell Cycle / Q000502:physiology*; D002460:Cell Line; D006224:Cricetinae; D004247:DNA; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D000882:Haplorhini; D006367:HeLa Cells; D006657:Histones / Q000235:genetics*; D006801:Humans; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000378:metabolism; D012097:Repressor Proteins; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
D004268:DNA-Binding Proteins; D006657:Histones; C494257:IRF1 protein, human; C494229:IRF2 protein, human; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D010750:Phosphoproteins; D012097:Repressor Proteins; D014157:Transcription Factors; D004247:DNA