Another promoter, located ~11 kb downstream of the NESP55 promoter, drives the expression of XLαs mRNA, which encodes a protein with partial identity to Gsα (Fig. 1). As in NESP55, the XLαs transcript uses a novel first exon (exon XL) that splices onto exons 2-13 of Gsα [36, 52]. Unlike in the case of NESP55, however, the in-frame termination codon for the XLαs transcript is the same as for Gsα, making the encoded XLαs and Gsα proteins identical over a long C-terminal stretch [64]. Exon XL and the XLαs promoter are located in a CpG island methylated on the maternal allele [36, 52]. Consistent with this epigenetic mark, XLαs is derived exclusively from the paternal allele in all investigated tissues [36, 52, 65]; however, variable biallelic expression of XLαs has been recently demonstrated in clonal bone stromal cells [47]. Most abundant expression of XLαs is detected in neuroendocrine tissues, particularly pituitary, but the expression of its mRNA is readily detected by Northern blot or RT-PCR in various tissues, including brain, pancreas, heart, kidney, and adipose tissue [36, 64, 66, 67]. As demonstrated in the rat nervous system, XLαs expression is developmentally regulated [68].
