Nucleic Acids Research, Vol 24, Issue 4 694-701, Copyright © 1996 by Oxford University Press
P Jansa and J Forejt
We have identified and characterized a novel retinoic acid (RA) response
element (Hi-RARE) in the second intron of the mouse major
histocompatibility H2Kb gene. The Hi-RARE sequence is conserved in all
mouse classical and Q class 1 genes, in MHC class 1 genes of the rat,
Rhesus macaque, cat and in the vast majority of human classical and non-
classical class 1 genes. The Hi-RARE sequence lies within a regulatory
element responsible for constitutive expression of a 5' enhancerless H2Kb
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 (PARs) 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 1 family genes.
ARTICLES
A novel type of retinoic acid response element in the second intron of the mouse H2Kb gene is activated by the RAR/RXR heterodimer
Laboratory of Mammalian Molecular Genetics, Institute of Molecular Genetics, Academy of Sciences of Czech Republic, Prague.
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