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FXR and RXRA binding in mouse liver

ABSTRACT: The Farnesoid-X-Receptor (FXR) is a nuclear receptor (NR) known to obligately heterodimerize with Retinoid-X-Receptor (RXR). FXR is expressed as four isoforms (α1-α4) that drive transcription from IR-1 (inverted repeat-1) DNA motifs. More recently, FXR isoforms α2/α4 were found to activate transcription predominantly from non-canonical ER-2 (everted repeat-2) DNA motifs, mediating most metabolic effects of general FXR activation.Here, we explored whether co-occupancy of FXR and RXR in the mouse liver has an influence on DNA motif binding preference. We found RXR acts as a molecular switch, promoting FXRα2 activation from IR-1 instead of ER-2 motifs. Our results showcase FXR as the first NR with RXR-dependent and independent modes of activation, highlighting a potential new layer of complexity for other RXR-heterodimerizing NRs.

ORGANISM(S): Mus musculus

PROVIDER: GSE261901 | GEO | 2024/03/20

REPOSITORIES: GEO

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