NDLI: LXRalpha functions as a cAMP-responsive transcriptional regulator of gene expression.

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LXRalpha functions as a cAMP-responsive transcriptional regulator of gene expression.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Yang, Z. Pratt, R. E. Chen, Y. E. Mu, H. Lopez-ilasaca, M. Dzau, V. J. Daviet, L. Chen, Q. Horiuchi, M. Tamura, K.
Description	Author Affiliation: Tamura K ( Cardiovascular Research, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.);
Abstract	LXRalpha is a member of a nuclear receptor superfamily that regulates transcription. LXRalpha forms a heterodimer with RXRalpha, another member of this family, to regulate the expression of cholesterol 7alpha-hydroxylase by means of binding to the DR4-type cis-element. Here, we describe a function for LXRalpha as a cAMP-responsive regulator of renin and c-myc gene transcriptions by the interaction with a specific cis-acting DNA element, CNRE (an overlapping cAMP response element and a negative response element). Our previous studies showed that renin gene expression is regulated by cAMP, at least partly, through the CNRE sequence in its 5'-flanking region. This sequence is also found in c-myc and several other genes. Based on our cloning results using the yeast one-hybrid system, we discovered that the mouse homologue of human LXRalpha binds to the CNRE and demonstrated that it binds as a monomer. To define the function of LXRalpha on gene expression, we transfected the renin-producing renal As4.1 cells with LXRalpha expression plasmid. Overexpression of LXRalpha in As4.1 cells confers cAMP inducibility to reporter constructs containing the renin CNRE. After stable transfection of LXRalpha, As4.1 cells show a cAMP-inducible up-regulation of renin mRNA expression. In parallel experiments, we demonstrated that LXRalpha can also bind to the homologous CNRE in the c-myc promoter. cAMP promotes transcription through c-myc/CNRE:LXRalpha interaction in LXRalpha transiently transfected cells and increases c-myc mRNA expression in stably transfected cells. Identification of LXRalpha as a cAMP-responsive nuclear modulator of renin and c-myc expression not only has cardiovascular significance but may have generalized implication in the regulation of gene transcription.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	15
Volume Number	97
Language	English
Publisher	National Academy of Sciences
Publisher Date	2000-08-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cyclic AMP Metabolism Receptors, Cytoplasmic And Nuclear Physiology Trans-Activators Transcriptional Activation Animals Cell Line Cell Nucleus Cloning, Molecular Cyclic AMP Response Element-Binding Protein DNA, Complementary DNA-Binding Proteins Mice Mice, Inbred DBA Molecular Sequence Data Orphan Nuclear Receptors Promoter Regions, Genetic Proto-Oncogene Proteins C-myc Genetics Renin Response Elements Saccharomyces Cerevisiae Transcription, Genetic Transfection Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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