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Tracking Operator State Fluctuations in Gene Expression in Single Cells

B. Banerjee ^*, S. Balasubramanian ^*, G. Ananthakrishna  , T. V. Ramakrishnan  and G. V. Shivashankar ^* 

^* National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India; Materials Research Centre, Centre for Condensed Matter Theory, Physics Department, Indian Institute of Science, Bangalore, India; and Raman Research Institute, Bangalore, India

Correspondence: Address reprint requests to G. V. Shivashankar, E-mail: shiva{at}ncbs.res.in.

We report the results of operator state fluctuations in gene expression for the entire bacterial growth cycle, using single-cell analysis and synthetic unregulated and negative-feedback transcription regulatory gene circuits. In the unregulated circuit, during the cell cycle, we observe a crossover from log-normal-to-normal distribution of expressed proteins and an unusual linear dependence of their standard deviation on the mean gene expression levels. With negative-feedback circuits we find the existence of bimodality as the cell cycle progresses. We suggest that such long-tail and bimodal distributions may be used as selection mechanisms in developmental switches and for assigning cell identity.

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