A retinoic acid-triggered cascade of HOXB1 gene activation.
Retinoic acid (RA) has been proposed to be a direct regulator of HOX gene complexes. However, the molecular mechanism of the RA signaling pathway during normal development is unclear. We have identified an RA-responsive element in the promoter of HOXB1 gene composed of two functionally separable sites: (i) a DR-2 sequence, which is the direct target of the RA receptor retinoid X receptor heterodimer; and (ii) a motif for an RA-inducible and tissue-specific coactivator termed retinoid-inducible protein. Through neither enhancer alone is functional, this combined element strongly activates the HOXB1 promoter in a cell-specific and retinoid-dependent manner. Finally, this activation is potentiated by a proximal autoregulatory site for HOXB1 gene itself. These data define a tripartite cascade leading to the establishment of HOXB1 gene activation.
Salk Institute for Biological Studies, La Jolla, CA 92037.
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D001483:Base Sequence; D004252:DNA Mutational Analysis; D005786:Gene Expression Regulation; D005801:Genes, Homeobox / Q000235:genetics*; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D047488:Retinoid X Receptors; D017384:Sequence Deletion; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D014212:Tretinoin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D018168:Receptors, Retinoic Acid; D011993:Recombinant Fusion Proteins; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014212:Tretinoin; D008156:Luciferases