E3, a hematopoietic-specific transcript directly regulated by the retinoic acid receptor alpha

Blood. 1996 Oct 1;88(7):2517-30.


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

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Differentiation
  • Cells, Cultured
  • Consensus Sequence
  • DNA, Complementary / genetics
  • Gene Expression Regulation / drug effects*
  • Genes, Immediate-Early*
  • Granulocytes / cytology
  • HL-60 Cells / drug effects
  • HL-60 Cells / metabolism
  • Hematopoietic Stem Cells / drug effects*
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Immediate-Early Proteins / biosynthesis
  • Immediate-Early Proteins / genetics*
  • Immediate-Early Proteins / physiology
  • Leukemia, Promyelocytic, Acute / pathology
  • Membrane Proteins
  • Mice
  • Molecular Sequence Data
  • Neoplasms / pathology
  • Phosphorylation
  • Promoter Regions, Genetic
  • Protein Processing, Post-Translational
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • RNA, Neoplasm / biosynthesis
  • RNA, Neoplasm / genetics
  • Receptors, Retinoic Acid / genetics
  • Receptors, Retinoic Acid / physiology*
  • Regulatory Sequences, Nucleic Acid
  • Retinoic Acid Receptor alpha
  • Sequence Homology, Nucleic Acid
  • Transfection
  • Tretinoin / pharmacology*


  • DNA, Complementary
  • Immediate-Early Proteins
  • Laptm5 protein, mouse
  • Membrane Proteins
  • RARA protein, human
  • RNA, Messenger
  • RNA, Neoplasm
  • Rara protein, mouse
  • Receptors, Retinoic Acid
  • Retinoic Acid Receptor alpha
  • Tretinoin

Associated data

  • GENBANK/U29489
  • GENBANK/U29539
  • GENBANK/U94402
  • GENBANK/U95002
  • GENBANK/U95003
  • GENBANK/U95004
  • GENBANK/U95005