Multiple mechanisms regulate the proliferation-specific histone gene transcription factor HiNF-D in normal human diploid fibroblasts

• Published in: Biochemistry (Easton) 1992-03, Vol.31 (10), p.2812-2818
• Main Authors: Wright, Kenneth L, Dell'Orco, Robert T, Van Wijnen, Andre J, Stein, Janet L, Stein, Gary S
• Format: Article
• Language: English
• Subjects: 550200 - Biochemistry; ANIMAL CELLS; BASIC BIOLOGICAL SCIENCES; BIOCHEMISTRY; Biological and medical sciences; Blood; CELL CYCLE; Cell Division; Cell Nucleus - metabolism; CHEMISTRY; CONNECTIVE TISSUE CELLS; Diploidy; DNA - biosynthesis; DNA REPLICATION; FIBROBLASTS; Fibroblasts - cytology; Fibroblasts - metabolism; Fundamental and applied biological sciences. Psychology; GENE REGULATION; GENE REPRESSORS; GENES; HISTONES; Histones - genetics; Humans; MESSENGER-RNA; Molecular and cellular biology; Molecular genetics; NUCLEIC ACID REPLICATION; NUCLEIC ACIDS; ORGANIC COMPOUNDS; RNA; SOMATIC CELLS; TRANSCRIPTION FACTORS; Transcription Factors - metabolism; Transcription, Genetic; Transcription. Transcription factor. Splicing. Rna processing
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi00125a023

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.