Stochastic patterns in globin gene expression are established prior to transcriptional activation and are clonally inherited

We have undertaken a detailed characterization of mouse globin gene expression patterns in the nucleus and cytoplasm of single erythroid cells. We demonstrate an imbalance of alpha- versus beta-globin expression in a significant proportion of cells both in nuclear transcription patterns and cytoplasmic mRNA levels. Clonal cell analysis showed these expression patterns to be clonally inherited, while analysis of a multicopy transgenic locus showed an all-or-none effect in the activation of all the genes in one locus. These data provide strong evidence for a stochastic basis of globin gene activation resulting in heritable all-or-none expression patterns.