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Publication : A novel type of retinoic acid response element in the second intron of the mouse H2Kb gene is activated by the RAR/RXR heterodimer.

First Author  Jansa P Year  1996
Journal  Nucleic Acids Res Volume  24
Issue  4 Pages  694-701
PubMed ID  8604312 Mgi Jnum  J:31599
Mgi Id  MGI:79085 Doi  10.1093/nar/24.4.694
Citation  Jansa P, et al. (1996) A novel type of retinoic acid response element in the second intron of the mouse H2Kb gene is activated by the RAR/RXR heterodimer. Nucleic Acids Res 24(4):694-701
abstractText  We have identified and characterized a novel retinoic acid (RA) response element (Hi-RARE) in the second intron of the mouse major histocompatibility H2K(b) gene. The Hi- RARE sequence is conserved in all mouse classical and Q class I genes, in MHC class I genes of the rat, Rhesus macaque, cat and in the vast majority of human classical and non-classical class I genes. The Hi-RARE sequence lies within a regulatory element responsible for constitutive expression of a 5' enhancerless H2K(b) gene in the Ltk(-) fibroblasts. Hi-RARE consists of two inverted palindromic RARE consensus sites (5'-PuGGTCA-3') separated by an 8 nt spacer. Mutational analysis revealed that both inverted palindromic hexanucleotide motifs are indispensable functional sites for the 9-cis RA response. The Hi-RARE sequence confers 9-cis RA inducibility to a heterologous promoter. The inducibility is further augmented in embryonal carcinoma cells by the expression of recombinant retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). In vitro, the recombinant RAR/RXR heterodimer creates DNA-protein complex with the Hi-RARE sequence. Treatment of P19 embryonal carcinoma cells with 9C-RA induces the Hi-RARE binding activity of nuclear proteins that proved to be RAR (or RAR-like)/RXR heterodimer. Thus the Hi-RARE represents a new type of RA response element with a role in the modulation of the expression of MHC class I family genes.
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