Abstract
Retinoic acid (RA)-induced maturation mediated by the retinoic acid receptor alpha (RAR alpha) has been implicated in myeloid development. We have used differential hybridization analysis of a cDNA library constructed from the murine RA-inducible MPRO promyelocyte cell line to identify immediate-early genes induced by RA during granulocytic differentiation. E3, one of nine sequences identified, was upregulated in an immediate-early manner, with transcript levels peaking after 60 minutes exposure to RA. E3 transcripts were RA-inducible in HL60 cells, but not in an RA-resistant subclone, HL60R, that harbors a mutated RAR alpha gene. However, when HL60R cells were transduced with a functional copy of the RAR alpha gene, RA induced a 10-fold increase in E3 mRNA levels. E3 transcripts are present in the myeloid, B-lymphoid, and erythroid lineages, absent in nonhematopoietic cells, and encode a highly hydrophobic, potentially phosphorylated polypeptide of unknown function with significant homology to a putative protein expressed in myeloid cells. The murine E3 promoter harbors a single bipartite retinoic acid response element which in transient transfection assays conferred RA sensitivity. These results indicate that E3 is a hematopoietic-specific gene that is an immediate target for the activated RAR alpha during myelopoiesis.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Base Sequence
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Cell Differentiation
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Cells, Cultured
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Consensus Sequence
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DNA, Complementary / genetics
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Gene Expression Regulation / drug effects*
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Genes, Immediate-Early*
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Granulocytes / cytology
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HL-60 Cells / drug effects
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HL-60 Cells / metabolism
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Hematopoietic Stem Cells / drug effects*
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Hematopoietic Stem Cells / metabolism
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Humans
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Immediate-Early Proteins / biosynthesis
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Immediate-Early Proteins / genetics*
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Immediate-Early Proteins / physiology
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Leukemia, Promyelocytic, Acute / pathology
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Membrane Proteins
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Mice
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Molecular Sequence Data
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Neoplasms / pathology
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Phosphorylation
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Promoter Regions, Genetic
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Protein Processing, Post-Translational
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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RNA, Neoplasm / biosynthesis
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RNA, Neoplasm / genetics
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Receptors, Retinoic Acid / genetics
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Receptors, Retinoic Acid / physiology*
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Regulatory Sequences, Nucleic Acid
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Retinoic Acid Receptor alpha
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Sequence Homology, Nucleic Acid
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Transfection
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Tretinoin / pharmacology*
Substances
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DNA, Complementary
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Immediate-Early Proteins
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Laptm5 protein, mouse
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Membrane Proteins
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RARA protein, human
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RNA, Messenger
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RNA, Neoplasm
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Rara protein, mouse
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Receptors, Retinoic Acid
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Retinoic Acid Receptor alpha
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Tretinoin
Associated data
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GENBANK/U29489
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GENBANK/U29539
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GENBANK/U94402
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GENBANK/U95002
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GENBANK/U95003
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GENBANK/U95004
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GENBANK/U95005