Nuclear orphan receptor-binding retinoic acid response elements in keratinocytes.

Keratinocytes are responsive cells for retinoic acid (RA) mediated signal transduction. In this study, we demonstrate binding of some important orphan receptors to previously identified retinoic acid response elements (RAREs) regulated by RA in keratinocytes. Using electrophoretic mobility shift assays (EMSAs) we show that in vitro translated ARP1 (apolipoprotein AI regulatory protein 1), EAR3 and EAR2 (v-erb A related genes) bind two RAREs. The RAREs investigated were previously identified in the VL30 retrotransposon (termed VLRRE2) and retinoic acid receptor beta 2 (termed RARE beta) genes, respectively. Furthermore, using an anti-ARP antibody that recognizes both ARP1 and EAR3 we show that these ARP subfamily member(s) present in keratinocytes bind to both RAREs. To our knowledge, this is the first demonstration of the binding of these proteins in keratinocytes to response elements regulated by RA in these cells. Our data suggest that ARP subfamily member(s) may modulate RA mediated transcription in epidermis.