TRANSCRIPTION OF INDIVIDUAL GENES IN EUKARYOTIC CELLS OCCURS RANDOMLYAND INFREQUENTLY

Experimental evidence is presented indicating that the expression of a lacZ reporter gene driven by the HIV-1 long terminal repeat in a seri es of stably transfected, cloned macrophage cell lines occurs in a ver y small proportion of cells. The proportion of cells expressing lacZ, rather than the level of expression in each cell, is regulated by exte rnal stimuli such as LPS and phorbol ester. Based upon these and publi shed data we propose that transcription in eukaryotic cells occurs in short pulses interspersed by long periods of inactivity of indetermina te duration. Transcriptional regulation is envisaged as involving chan ges in the probability rather than the rate of transcription. A probab ilistic model of transcription may explain many biological phenomena, such as stem cell division and clonogenic activity, heterogeneous gene expression among clonal cell populations, retroviral latency and cell cycle progression, which appear to involve stochastic decisions.