Nucleic Acids Research, Vol 24, Issue 13 2511-2518, Copyright © 1996 by Oxford University Press
TR Bishop, MW Miller, J Beall, LI Zon and P Dierks
In an effort to understand how the heme biosynthetic pathway is uniquely
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 first exons,
named 1A and 1B, which are alternatively spliced to exon 2, where the
coding region begins. Each first exon has its own promoter. The 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 genes. Tissue
distribution studies reveal that ALAD mRNA containing axon 1A is
ubiquitous, whereas mRNA containing axon 1B is found only in erythroid
tissues. This finding, together with our further observation that GATA-1
mRNA levels increase 3-fold during maturation of murine erythroid
progenitor cells, may help explain simultaneous 3-fold increases in exon 1B
expression. The unexpected result that axon 1A expression 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 position analogous to the
NF-E2 site in the locus control region of the beta-globin gene cluster.
ARTICLES
Genetic regulation of delta-aminolevulinate dehydratase during erythropoiesis
Department of Pediatric Hematology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
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