LOCUS-CONTROL REGIONS - OVERCOMING HETEROCHROMATIN-INDUCED GENE INACTIVATION IN MAMMALS

Differentiation of specific cell types during the development of mamma ls requires the selective silencing or activation of tissue-specific g enes, Locus control regions (LCRs) are gene regulatory elements that a ct in cis to ensure that active transcriptional units are established in all cells of a given cell lineage. Over the past year, it has becom e clear that this process takes place at the level of chromatin remode lling, and that LCRs ensure that this decision is made by both alleles in every cell. Studies on LCRs and analysis of gene expression in tra nsgenic mice at the single cell level has revealed that the breakdown in LCR function accompanying the deletion of specific sequences result s in a phenomenon known as position effect variegation, described in d etail in yeast and Drosophila. Thus, when located in close proximity t o heterochromatin a transgene linked to a disabled LCR is randomly sil enced in a proportion of cells. This finding implies that all subregio ns within an LCR are necessary to ensure the establishment of an open chromatin configuration of a gene even when the latter is located in a highly heterochromatic region.