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J. Biol. Chem., Vol. 278, Issue 17, 15252-15260, April 25, 2003

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Identification of a Novel Set of Genes Regulated by a Unique Liver X Receptor--mediated Transcription Mechanism^*

Leonard M. Anderson, Sung E. Choe^§, Rustam Y. Yukhananov^¶, Rob L. Hopfner, George M. Church^§, Richard E. Pratt, and Victor J. Dzau

From the  Department of Medicine, Division of Cardiovascular Research, Laboratory of Genetic Physiology, the ^§ Department of Medicine, Division of Genetics, and the ^¶ Department of Anesthesiology, Neurogenomic Laboratory, Pain Research Center, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115

We have reported previously that liver X receptor- (LXR) 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 cAMP-negative response element (CNRE). To determine whether this novel action of LXR 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 LXR binding via electrophoretic mobility shift assays (EMSA) 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 LXR and the CNRE enhancer element is responsible for widespread changes in gene expression and identify a set of LXR/cAMP-regulated genes that may have important biological implications.

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