Abstract
Transcription factor GATA-1 is essential for normal erythropoiesis. GATA-binding sites are consistently found in promoters or enhancers of genes expressed selectively in erythroid cells. To discover novel GATA-1-regulated genes, we searched for GATA-1-activated transcripts in G1E cells, an erythroid line derived from GATA-1(-) embryonic stem cells. By subtractive analysis, we identified a new ATP-binding cassette (ABC) transporter that is strongly and rapidly induced by GATA-1. This protein, named ABC-me (for ABC-mitochondrial erythroid), localizes to the mitochondrial inner membrane and is expressed at particularly high levels in erythroid tissues of embryos and adults. ABC-me is induced during erythroid maturation in cell lines and primary hematopoietic cells, and its overexpression enhances hemoglobin synthesis in erythroleukemia cells. The ABC proteins participate in diverse physiological processes by coupling ATP hydrolysis to the transport of a variety of substrates across cell membranes. We speculate that ABC-me, a newly identified erythroid-expressed ABC superfamily member, may mediate critical mitochondrial transport functions related to heme biosynthesis.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP-Binding Cassette Transporters*
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Amino Acid Sequence
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Animals
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Carrier Proteins / biosynthesis
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Carrier Proteins / genetics
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Carrier Proteins / isolation & purification*
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Cell Differentiation
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Cell Line
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DNA, Complementary / genetics
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DNA-Binding Proteins / physiology*
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Erythroid Precursor Cells / cytology
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Erythroid Precursor Cells / metabolism*
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Erythroid-Specific DNA-Binding Factors
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Erythropoiesis / genetics*
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Fetal Proteins / biosynthesis
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Fetal Proteins / genetics
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GATA1 Transcription Factor
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Gene Expression Regulation, Developmental*
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Genes, Reporter
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Hematopoietic System / embryology
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Hematopoietic System / growth & development
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Heme / physiology
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Hemoglobins / biosynthesis
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Hemoglobins / genetics
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Intracellular Membranes / metabolism
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Leukemia, Erythroblastic, Acute / pathology
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Membrane Proteins / biosynthesis
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Membrane Proteins / genetics
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Membrane Proteins / isolation & purification*
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Mice
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Mitochondria / metabolism*
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Models, Molecular
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Molecular Sequence Data
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Polymerase Chain Reaction
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Promoter Regions, Genetic / genetics
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Rats
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Recombinant Fusion Proteins / biosynthesis
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Sequence Alignment
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Sequence Homology, Amino Acid
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Transcription Factors / physiology*
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Transcription, Genetic
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Tumor Cells, Cultured
Substances
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ATP-Binding Cassette Transporters
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Abcb10 protein, mouse
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Carrier Proteins
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DNA, Complementary
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DNA-Binding Proteins
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Erythroid-Specific DNA-Binding Factors
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Fetal Proteins
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GATA1 Transcription Factor
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Gata1 protein, mouse
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Gata1 protein, rat
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Hemoglobins
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Membrane Proteins
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Recombinant Fusion Proteins
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Transcription Factors
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Heme