Project: Research project

Project Details


Glucocorticoids regulate the transcription of rDNA in lymphosarcoma P1798
cells in culture. Sixteen-hour treatment with 0.1 micromolar dexamethasone
causes 95% inhibition of synthesis of pre-rRNA in intact cells and a
corresponding decrease in the rate of initiation upon the cloned mouse rRNA
promoter and upon nucleolar chromatin. This does not result from a direct
interaction between the glucocorticoid receptor and the gene. Rather,
glucocorticoids regulate the expression of one or more transcription
initiation factors. A partially purified initiation factor from control
cells is capable of reconstituting transcription of the cloned rRNA
promoter. This factor is not required for the formation of stable
pre-initiation complexes. Extracts from control and hormone-treated cells
are capable of forming approximately 10 -19 mol of pre-initiation
complex/microliter of extract. In control extracts, the pre-initiation
complex is converted to a heparin-resistant initiation complex at a rate of
about 2x10 -20 mol/sec, and the calculated rate of elongation from such
initiation complexes approximates the rate of elongation determined upon
homopolymerically tailed templates (approximately 25 nt/sec). Formation of
heparin-resistant initiation complexes does not occur at a detectable rate
in extracts from hormone-treated cells. However, the rate of elongation by
RNA polymerase I from hormone-treated cells is approximately 25 nt/sec on
homopolymerically tailed templates. Our working hypothesis is that
transcription of cloned rDNA proceeds by a two-step reaction. The first
reaction involves the formation of stable pre-initiation complexes and
proceeds at a rate that is at least an order of magnitude slower than the
steady state rate of transcription. Under steady state conditions, the
rate of transcription is limited by the amount of a protein(s) that is
required for formation of heparinresistant initiation complexes. This
protein is subject to regulation by glucocorticoids in lymphosarcoma
cells. (C)
Effective start/end date9/30/786/30/91


  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health


  • Medicine(all)


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