THE A-GAMMA-GLOBIN 3'-ELEMENT PROVIDES NO UNIQUE FUNCTION(S) FOR HUMAN BETA-GLOBIN LOCUS GENE-REGULATION

The human beta-globin locus is activated transcriptionally by a comple x series of events that culminate in appropriate temporal and tissue-s pecific control over five separate genes during embryonic and early po stnatal development. One cis-regulatory element in the locus, original ly identified as an enhancer 3' to the A gamma-globin gene, more recen tly has been suggested to harbor alternative or additional properties, including stage-specific silencer, insulator, nuclear matrix, or chro mosome scaffold attachment activities. W\e have re-evaluated the activ ity during erythropoiesis that is conferred by this element by deletin g it from a yeast artificial chromosome (YAC) containing the entire hu man beta-globin locus and then assaying for the expression of each gen e at each developmental stage after incorporation of the mutant YAC in to the mouse germline. The data show that loss of the A gamma-globin 3 ' element confers no phenotype in six independent lines of intact YAC mutant transgenic mice, thus demonstrating (minimally) that any activi ties attributable to this element are fully compensated by other DNA s equences within the beta-globin locus.