Identification of a Novel Set of Genes Regulated by a Unique LXRα-Mediated Transcription Mechanism

Running Title: LXRα Regulated Genes in As4.1 cells 2 SUMMARY We have reported previously that LXRα can mediate a novel cAMP dependent increase in renin and c-myc gene transcription by binding as a monomer to a unique regulatory element, termed the CNRE. To determine if this novel action of LXRα has global implications on gene regulation, we employed expression profiling to identify other genes regulated by this unique mechanism. Here we report the existence of a set of known and unknown transcripts regulated in parallel with renin. Querying the Celera Mouse Genome Assembly revealed that a majority of these genes contained the consensus CNRE. We have confirmed the functionality of these CNREs by competition for LXRα binding via EMSA assays, and by the use of CNRE decoy molecules documenting the abolishment of the cAMP-mediated gene induction. Taken together, these results demonstrate that the interaction between cAMP-activated LXRα and the CNRE enhancer element is responsible for widespread changes in gene expression and identify a set of LXRα/cAMP regulated genes that may have important biological implications.