Organization, Sequence, Chromosomal Localization, and Promoter Identification of the Mouse Orphan Nuclear Receptor Nurr1 Gene

We have cloned and characterized the organization of the mouse orphan nuclear receptor Nurr1 gene. The Nurr1 gene is approximately 7 kb long, contains eight exons and seven introns, and mapped to mouse chromosome 2. Although the exon/intron structure of Nurr1 is nearly identical to that of Nur77, Nurr1 possesses an additional untranslated exon. Primer extension was used to identify two major transcription initiation sites mapped 37 nucleotides apart in the first untranslated exon. Functional studies of chimeric Nurr1–luciferase reporter genes delineated the promoter region and underscored the importance of the +1 transcription start site. Sequence analysis of the 5′ flanking region surrounding +1 revealed several possible response elements such as a hexanucleotide glucocorticoid binding site, a cAMP-response element, a CArG box, and two c-Jun-binding sites. These data help to explain the different response characteristics of two closely related early response genes, Nurr1 and Nur77.