Identification of a novel set of genes regulated by a unique liver X receptor-alpha -mediated transcription mechanism.
We have reported previously that liver X receptor-alpha (LXRalpha) 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 LXRalpha 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 LXRalpha 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 LXRalpha and the CNRE enhancer element is responsible for widespread changes in gene expression and identify a set of LXRalpha/cAMP-regulated genes that may have important biological implications.
Anderson
Leonard M
LM
Department of Medicine, Division of Cardiovascular Research, Laboratory of Genetic Physiology, Pain Research Center, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Choe
Sung E
SE
Yukhananov
Rustam Y
RY
Hopfner
Rob L
RL
Church
George M
GM
Pratt
Richard E
RE
Dzau
Victor J
VJ
D000818:Animals; D001665:Binding Sites; D016000:Cluster Analysis; D016384:Consensus Sequence; D000242:Cyclic AMP / Q000494:pharmacology; D004268:DNA-Binding Proteins; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D000071518:Liver X Receptors; D051379:Mice; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D012083:Renin / Q000235:genetics; D020218:Response Elements; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D000242:Cyclic AMP; D012083:Renin