TY - JOUR
T1 - Structure and regulation of the chicken erythroid δ-aminolevulinate synthase gene
AU - Lim, Kim chew
AU - Ishihara, Hajime
AU - Riddle, Robert D.
AU - Yang, Zhuoying
AU - Andrews, Nancy
AU - Yamamoto, Masayuki
AU - Engel, James Douglas
N1 - Funding Information:
We thank Drs Norio Hayashi, Linda Ko, Mark W.Leonard, Masuo Obinata and Matthew Roth for careful reading and constructive criticism of the manuscript. We also thank Susan J.Stamler and Daniel B.Oerther for excellent technical assistance. This work was supported in part by NIH grants (HL 24415 and HL 45168; J.D.E.) and from the Ministry of Education, Science and Culture and Uehara Memorial Foundation (M.Y.). We dedicate this paper to the memory of Dr David Shemin, who discovered ALA synthase, and whose life's work was devoted to elucidating the multiple facets of heme biosynthesis as well as to nurturing the interests of his younger colleagues in this and other fascinating aspects of biochemistry.
PY - 1994/4/11
Y1 - 1994/4/11
N2 - 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 δ-amlnolevullnate synthase (ALAS-N) in all non-erythrold cells, the expression of an erythroid-speclfic isozyme (ALAS-E) is developmentally regulated in red blood cells. As a first step towards understanding the molecular basis for the transcrlptional regulation of ALAS-E during erythropolesis, 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 contiguous exons and is predicted to form a very stable stem-loop structure that bears resemblance to the ferrltln iron-responsive element. Tissue-specific expression of the ALAS-E gene was analyzed by transient transfectlon assays in hematopoietlc 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-speclfic transcription.
AB - 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 δ-amlnolevullnate synthase (ALAS-N) in all non-erythrold cells, the expression of an erythroid-speclfic isozyme (ALAS-E) is developmentally regulated in red blood cells. As a first step towards understanding the molecular basis for the transcrlptional regulation of ALAS-E during erythropolesis, 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 contiguous exons and is predicted to form a very stable stem-loop structure that bears resemblance to the ferrltln iron-responsive element. Tissue-specific expression of the ALAS-E gene was analyzed by transient transfectlon assays in hematopoietlc 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-speclfic transcription.
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U2 - 10.1093/nar/22.7.1226
DO - 10.1093/nar/22.7.1226
M3 - Article
C2 - 8165137
AN - SCOPUS:0028298521
VL - 22
SP - 1226
EP - 1233
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 7
ER -