Transcriptional regulation of a Purkinje cell-specific gene through a functional interaction between ROR alpha and RAR.

BACKGROUND

The orphan nuclear receptor ROR alpha is highly expressed in the Purkinje cells of the cerebellum during the postnatal development of brain. A recent observation has been made that the ROR alpha gene is disrupted in staggerer mice-which show a cell-autonomous defect in the development of the Purkinje cells.

RESULTS

In order to understand the functions of ROR alpha in cerebellar development, I attempted to identify its target genes. Transient expression study demonstrated that transcription of the Purkinje cell protein-2 (Pcp-2) gene is activated by ROR alpha, which binds as a monomer to a single half-site motif (RORE) within the promoter region. Its transcription was also activated by retinoic acid receptor (RAR) which binds as a heterodimer with RXR to a retinoic acid responsive element (RARE) in the downstream region. Interestingly, the ROR alpha-mediated transcription is further activated synergistically by RAR.

CONCLUSION

That the Pcp-2 gene is a target of ROR alpha, and is suggested that its transcription is also regulated by RAR.