Expression of the murine Nr4a1 gene is controlled by three distinct genomic loci

The transcription factor NR4A1 belongs to the class of orphan nuclear receptors without known ligand which might control its activity. Here we examined its transcriptional regulation in response to elevated cAMP levels in HL-1 cardiac myocytes and in the heart in vivo. We report, that murine Nr4a1 is expressed from distinct promoters located upto − 11.5 kb from the first coding exon. Whereas in HL-1 cells only two of the three distinct transcripts were induced by cAMP, in the heart all transcripts were regulated in response to β-adrenergic stimulation.

► Identification of two novel transcripts for murine orphan receptor Nr4a1 ► Transcriptional initiation from distinct genomic loci via alternative splicing ► In vivo ß-adrenergic stimulation displayed functionality of novel transcripts ► cAMP-stimulation in cardiac HL1-cells showed differential regulation of transcripts ► Represents a cell-type and metabolic state specific regulatory mechanism for Nr4a1