Molecular mechanisms of extinction: old findings and new ideas

Fusion experiments between somatic cells have been used for a long time as a means to understand the regulation of gene expression. In hybrids between differentiated cells such as hepatocytes or lymphocytes and undifferentiated cells such as fibroblasts a phenomenon called extinction has been described. In such hybrids expression of cell-specific genes derived from the more differentiated parental cell is selectively turned off (extinguished), whereas genes expressed from both cells like housekeeping genes remain active after fusion. Study of the molecular basis of extinction of the liver-specifically expressed tyrosine aminotransferase gene and of the B-cell-specifically expressed immunoglobulin genes has revealed that in hybrids the transcriptional program of the differentiated cells is reset. This is accompanied by a loss of expression or activity of many of the regulatory molecules that were operating in the differentiated cells. In the light of new insights in eukaryotic gene regulation we speculate that molecular mechanisms such as chromatin remodelling, recruitment to heterochromatin or subnuclear localization could underly the extinction process.