Analysis and Modeling of Early Estradiol-induced GREB1 Single Allele Gene Transcription at the Population Level.

After application of a gene transcription stimulus, in this case the hormone 17 -estradiol, on large populations of cells over a short time period, we focused on quantifying and modeling the frequencies of GREB1 single allele activations. We have established an experimental and computational pipeline to analyze large numbers of high resolution smFISH images to detect and monitor active GREB1 alleles, that can be translatable to any target gene of interest. A key result is that, at the population level, activation of individual GREB1 alleles within the same nucleus do exhibit which we quantify by the between activation states of pairs of alleles. After noticing that frequencies of joint alleles activations observed over our large cell populations evolve smoothly in time, we have defined a which we fit to the observed time course of GREB1 activation frequencies. This provided coherent estimates of the mean time between rounds of GREB1 transcription and the mean lifetime of nascent mRNAs. Our algorithmic approach and experimental methods are applicable to many other genes.