RXREs

RXREs, or Retinoid X receptor response elements, are cis-regulatory DNA sequences found in the promoters or enhancers of target genes. They mediate transcriptional responses to ligands of the retinoid X receptor (RXR) family, functioning either as RXR homodimers or as parts of heterodimers with other nuclear receptors.

The exact sequence of RXREs varies by locus and partner receptor, but many RXREs are palindromic or direct-repeat motifs. Arrangements such as direct repeats separated by one to five nucleotides (DR1, DR2, DR5) are common, reflecting the preference of different RXR-containing dimers for particular spacings. The RXR subunit provides a conserved DNA-binding half-site that contributes to dimer recognition.

Mechanistically, RXR-containing dimers bind RXREs in chromatin and recruit coactivator or corepressor complexes to regulate transcription. Ligand binding to RXR or its partner receptor induces conformational changes that alter DNA binding and transcriptional output, enabling integration of retinoid signals with lipid and metabolic pathways.

Biological roles include regulation of genes implicated in development, metabolism, and cellular differentiation. RXRE-regulated networks are conserved across vertebrates, with particular importance in lipid homeostasis, adipogenesis, and energy balance.

In research and medicine, RXREs are used to study nuclear receptor signaling and as targets in metabolic disorders and cancer. They are also exploited in reporter assays to investigate receptor activity and ligand specificity.

See also: Retinoid X receptor, Nuclear receptor, Retinoic acid receptor, Hormone response element, DR motif.