PMID- 8604312 OWN - NLM STAT- MEDLINE DCOM- 19960515 LR - 20190501 IS - 0305-1048 (Print) IS - 1362-4962 (Electronic) IS - 0305-1048 (Linking) VI - 24 IP - 4 DP - 1996 Feb 15 TI - A novel type of retinoic acid response element in the second intron of the mouse H2Kb gene is activated by the RAR/RXR heterodimer. PG - 694-701 AB - 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. FAU - Jansa, P AU - Jansa P AD - Laboratory of Mammalian Molecular Genetics, Institute of Molecular Genetics, Academy of Sciences of Czech Republic, Prague. FAU - Forejt, J AU - Forejt J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Nucleic Acids Res JT - Nucleic acids research JID - 0411011 RN - 0 (Receptors, Retinoic Acid) RN - 0 (Recombinant Proteins) RN - 0 (Retinoid X Receptors) RN - 0 (Transcription Factors) RN - 5688UTC01R (Tretinoin) SB - IM MH - Animals MH - Base Sequence MH - Conserved Sequence MH - Introns/genetics MH - Major Histocompatibility Complex/*genetics MH - Mice MH - Molecular Sequence Data MH - Mutation MH - Receptors, Retinoic Acid/*genetics/metabolism MH - Recombinant Proteins/genetics/metabolism MH - Retinoid X Receptors MH - Sequence Alignment MH - Transcription Factors/*genetics/metabolism MH - Tretinoin/*metabolism PMC - PMC145677 EDAT- 1996/02/15 00:00 MHDA- 1996/02/15 00:01 PMCR- 1996/02/15 CRDT- 1996/02/15 00:00 PHST- 1996/02/15 00:00 [pubmed] PHST- 1996/02/15 00:01 [medline] PHST- 1996/02/15 00:00 [entrez] PHST- 1996/02/15 00:00 [pmc-release] AID - 5b0246 [pii] AID - 10.1093/nar/24.4.694 [doi] PST - ppublish SO - Nucleic Acids Res. 1996 Feb 15;24(4):694-701. doi: 10.1093/nar/24.4.694.