GENETIC-REGULATION OF DELTA-AMINOLEVULINATE DEHYDRATASE DURING ERYTHROPOIESIS

In an effort to understand how the heme biosynthetic pathway is unique ly regulated in erythroid cells, we examined the structure of the gene encoding murine delta-aminolevulinate dehydratase (ALAD; EC4.2.1.24), which is the second enzyme of the pathway, The gene contains two firs t exons, named 1A and 1B, which are alternatively spliced to exon 2, w here the coding region begins, Each first exon has its own promoter, T he promoter driving exon 1A expression is TATA-less and contains many GC boxes, In contrast, the exon 1B promoter bears regulatory sequences similar to those found for beta-globin and other erythroid-specific g enes, Tissue distribution studies reveal that ALAD mRNA containing exo n 1A is ubiquitous, whereas mRNA containing exon 1B is found only in e rythroid tissues, This finding, together with our further observation that GATA-1 mRNA levels increase 3-fold during maturation of murine er ythroid progenitor cells, may help explain simultaneous 3-fold increas es in exon 1B expression, The unexpected result that exon 1A expressio n also increases 3-fold during CFU-E maturation may be attributable to the action of NF-E2, since there is a potential binding site in a pos ition analogous to the NF-E2 site in the locus control region of the b eta-globin gene cluster.