E3, A HEMATOPOIETIC-SPECIFIC TRANSCRIPT DIRECTLY REGULATED BY THE RETINOIC ACID RECEPTOR-ALPHA

Retinoic acid (RA)-induced maturation mediated by the retinoic acid re ceptor alpha (RAR alpha) has been implicated in myeloid development. W e have used differential hybridization analysis of a cDNA library cons tructed from the murine RA-induced MPRO promyelocyte cell line to iden tify immediate-early genes induced by RA during granulocytic different iation. E3, one of nine sequences identified, was upregulated in an im mediate-early manner, with transcript levels peaking after 60 minutes exposure to RA. E3 transcripts were RA-inducible HL60 cells, but not i n an RA-resistant subclone, HL60R. that harbors a mutated RAR alpha ge ne. However. when HL60R cells were transduced with a functional copy o f 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 hydrop hobic, 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 resp onse element which in transient transfection assays conferred RA sensi tivity. These results indicate that E3 is a hematopoietic-specific gen e that is an immediate target for the activated RAR alpha during myelo poiesis. (C) 1996 by The American Society of Hematology.