Structure and regulation of the chicken erythroid delta-aminolevulinate synthase gene.
Erythroid cells regulate heme biosynthesis in a manner that is distinct from all other cell types. While heme negatively regulates the synthesis of the housekeeping delta-aminolevulinate synthase (ALAS-N) in all non-erythroid cells, the expression of an erythroid-specific isozyme (ALAS-E) is developmentally regulated in red blood cells. As a first step towards understanding the molecular basis for the transcriptional regulation of ALAS-E during erythropoiesis, we cloned and characterized the chicken ALAS-E locus. This gene spans 18 kbp and is composed of eleven exons. The intron/exon structure of erythroid ALAS was found to be conserved among several vertebrate species. Direct RNA sequencing identified a 5' untranslated region that is derived from two continuous exons and is predicted to form a very stable stem-loop structure that bears resemblance to the ferritin iron-responsive element. Tissue-specific expression of the ALAS-E gene was analyzed by transient transfection assays in hematopoietic cells of both erythroid and non-erythroid origins. These experiments identified distal (-784 to -505 bp) and proximal (-155 to +21 bp) promoter elements which are required for high level, erythroid-specific transcription.
Lim
K C
KC
Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, IL 60208.
Ishihara
H
H
Riddle
R D
RD
Yang
Z
Z
Andrews
N
N
Yamamoto
M
M
Engel
J D
JD
D000624:5-Aminolevulinate Synthetase / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D002645:Chickens; D004247:DNA; D004912:Erythrocytes / Q000166:cytology / Q000201:enzymology*; D005091:Exons; D015971:Gene Expression Regulation, Enzymologic; D006418:Heme / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic
D006418:Heme; D004247:DNA; D000624:5-Aminolevulinate Synthetase