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

ABSTRACT: 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.

SUBMITTER: Jansa P

PROVIDER: S-EPMC145677 | biostudies-other | 1996 Feb

REPOSITORIES: biostudies-other

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

Jansa P P Forejt J J

Nucleic acids research 19960201 4

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 ...[more]

PMID: 8604312

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Project description:Differentiation of embryonic and adult myogenic progenitors undergoes a complex series of cell rearrangements and specification events which are controlled by distinct gene regulatory networks. Delineation of the molecular mechanisms that regulate skeletal muscle specification and formation should be important for understanding congenital myopathies and muscular degenerative diseases. Retinoic acid (RA) signaling plays an important role in development. However, the role of RA signaling in adult myogenic progenitors is poorly understood. Here, we investigate the role of RA signaling in regulating myogenic differentiation of myoblastic progenitor cells. Using the mouse myoblast progenitor C2C12 line as a model, we have found that the endogenous expression of most RAR and RXR isotypes is readily detected. While the nuclear receptor co-repressors are highly expressed, two of the three nuclear receptor co-activators and the enzymes involved in RA synthesis are expressed at low level or undetectable, suggesting that the RA signaling pathway may be repressed in myogenic progenitors. Using the alpha-myosin heavy chain promoter-driven reporter (MyHC-GLuc), we have demonstrated that either ATRA or 9CRA is able to effectively induce myogenic differentiation, which can be synergistically enhanced when both ATRA and 9CRA are used. Upon ATRA and 9CRA treatment of C2C12 cells the expression of late myogenic markers significantly increases. We have further shown that adenovirus-mediated exogenous expression of RARalpha and/or RXRalpha is able to effectively induce myogenic differentiation in a ligand-independent fashion. Morphologically, ATRA- and 9CRA-treated C2C12 cells exhibit elongated cell body and become multi-nucleated myoblasts, and even form myoblast fusion. Ultrastructural analysis under transmission electron microscope reveals that RA-treated myogenic progenitor cells exhibit an abundant presence of muscle fibers. Therefore, our results strongly suggest that RA signaling may play an important role in regulating myogenic differentiation.

Dataset Information

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

Publications

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

Similar Datasets

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