TRANSCRIPTOME 2002: From Functional Genomics to Systems Biology
March 10-13, 2002
Seattle, Washington, USA

Globin Gene Activation: A Stochastic Process

Frank Grosveld, Mariken de Krom, Mariette van de Corput, and John Strouboulis, Dept. of Cell Biology, Erasmus University, Rotterdam, THE NETHERLANDS

Models for stochastic gene activation have been invoked to explain mono-allelic expression patterns of genes involved in immune and cellular responses, dosage compensation and cell commitment, but have also been proposed for gene activation in general. We have tested the generality of a stochastic model at the allelic level using the alpha and beta globin genes, as they play no role in any cellular selection processes. Allelic transcription patterns and mRNA levels in single cells showed an imbalance of alpha versus beta globin expression in a significant proportion of cells and different probabilities in the activation of alpha and beta globin genes.Interestingly once a cell chooses a particular pattern of expression, that pattern becomes fixed in the cell. These data provide strong evidence for a stochastic basis of gene activation in general, which has broad implications for a variety of processes from the evolution of different layers of gene control to phenotypic differences between genetically identical cells and organisms.

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