Multiple mechanisms regulate the proliferation-specific histone gene transcription factor HiNF-D in normal human diploid fibroblasts.
The proliferation-specific transcription factor complex HiNF-D interacts with sequence specificity in a proximal promoter element of the human H4 histone gene FO108, designated Site II. The occupancy of Site II by HiNF-D has been implicated in proper transcription initiation and as a component of the cell cycle regulation of this gene. In the present study we have investigated the role of the HiNF-D/Site II interaction in controlling the level of H4 histone gene transcription during modifications of normal cellular growth. HiNF-D binding activity is present at high levels in rapidly proliferating cultures of human diploid fibroblasts and is reduced to less than 2% upon the cessation of proliferation induced by serum deprivation of sparsely population fibroblast cultures. Density-dependent quiescence also abolishes HiNF-D binding activity. Downregulation of transcription from the H4 gene occurs concomitant with the loss of the HiNF-D/Site II interaction, further suggesting a functional relationship between Site II occupancy and the capacity for transcription. Serum stimulation of quiescent preconfluent cells results in an increase in HiNF-D binding activity as the cells are resuming DNA synthesis and H4 histone gene transcription. Density-inhibited quiescent cells respond to serum stimulation with only a minimal increase in the HiNF-D binding activity, 30% of maximal levels. However, H4 histone gene transcription is stimulated to a level equal to that detected in extracts of the sparsely populated serum-stimulated cultures. These results suggest that there is a threshold level of HiNF-D binding activity necessary for the activation of H4 histone gene transcription.(ABSTRACT TRUNCATED AT 250 WORDS)
Wright
K L
KL
Department of Cell Biology, University of Massachusetts Medical Center, Worcester 01655.
Dell'Orco
R T
RT
van Wijnen
A J
AJ
Stein
J L
JL
Stein
G S
GS
D001769:Blood; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004171:Diploidy; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006657:Histones / Q000235:genetics*; D006801:Humans; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D006657:Histones; D014157:Transcription Factors; D004247:DNA