RANDOM ACTIVATION OF A TRANSGENE UNDER THE CONTROL OF A HYBRID HCD2 LOCUS-CONTROL REGION IG ENHANCER REGULATORY ELEMENT

Locus control regions such as those of human CD2 and beta-globin diffe r from classical enhancers in that, whereas the former confer high lev el, copy-dependent, position-independent expression to linked genes in transgenic mice, the latter do not, expression levels being dependent on the site of integration. We report that the position independence of the CD2 locus control region is modified by coupling it to the immu noglobulin heavy chain enhancer. Whilst in the majority of transgenic lines the Ig heavy chain enhancer has little or no effect on T cell ex pression of the hCD2 transgene, in others transgene expression is non- specifically extinguished in a proportion of lymphoid cells. The trans genic locus chromatin appears inaccessible to DNase I in these cells, which do not express the gene. Furthermore, mice homozygous for the hy brid hCD2 - Ig heavy chain enhancer construct contain T cells with bot h an active and an inactive transgene. The 'decision' to express or re press the gene appears to be a random process which involves each chro mosome separately, occurs at early stages in differentiation and is he ritable by daughter cells. These data suggest the possibility that sto chastic decisions might control a number of biological processes.