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

Journal Article · Tue Mar 17 04:00:00 EST 1992 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00125a023· OSTI ID:5562670

Wright, K L; van Wijnen, A D; Stein, J L; Stein, G S ^[1]; Dell'Orco, R T ^[2]

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1. Univ. of Massachusetts Medical Center, Worcester (United States)
2. Samuel Roberts Noble Foundation, Inc., Ardmore, OK (United States)

The proliferation-specific transcription factor complex HiNF-D interacts 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 the authors have investigated the role of the HiNF-D/Site II interaction in controlling the level of H4 histone gene transcription during modification 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 populated fibroblast cultures. Density-dependent quiescence also abolished HiNF-D binding activity. These results suggest that there is a threshold level of HiNF-D binding activity necessary for the activation of H4 histone gene transcription. Additionally, these findings suggest that there may be a mechanism repressing HiNF-D binding activity in the density-inhibited cultures which is not operative in the sparsely populated, serum-deprived cultures. Density-inhibited cultures may have reached a state analogous to the initial steps of differentiation and have invoked a series of mechanisms to decrease expression of proliferation-specific factors. These results are consistent with the presence of at least two levels of control over the HiNF-D/Site II interaction which are responsive to and reflect the proliferative state of the cell and the extent to which the cell exhibits properties associated with differentiation.

• OSTI ID: 5562670
• Journal Information: Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 31:10; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
BIOCHEMISTRY
CELL CYCLE
CHEMISTRY
CONNECTIVE TISSUE CELLS
DNA REPLICATION
FIBROBLASTS
GENE REGULATION
GENE REPRESSORS
GENES
HISTONES
MESSENGER-RNA
NUCLEIC ACID REPLICATION
NUCLEIC ACIDS
ORGANIC COMPOUNDS
RNA
SOMATIC CELLS
TRANSCRIPTION FACTORS