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Liver X receptors (LXRα and LXRβ) are potent regulators for hepatic Dec1 expression
Author(s) -
Noshiro Mitsuhide,
Usui Emiko,
Kawamoto Takeshi,
Sato Fuyuki,
Nakashima Ayumu,
Ueshima Taichi,
Honda Kiyomasa,
Fujimoto Katsumi,
Honma Sato,
Honma Kenichi,
Makishima Makoto,
Kato Yukio
Publication year - 2009
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2008.01247.x
Subject(s) - liver x receptor , biology , per1 , transcription factor , nuclear receptor , circadian clock , hepatocyte nuclear factor 4 , chromatin immunoprecipitation , enhancer , circadian rhythm , clock , microbiology and biotechnology , medicine , gene expression , endocrinology , promoter , biochemistry , gene
DEC1 (BHLHB2/Stra13/Sharp2)—a basic helix‐loop‐helix transcription factor—is known to be involved in various biological phenomena including clock systems and metabolism. In the clock systems, Dec1 expression is dominantly up‐regulated by CLOCK : BMAL1 heterodimer, and it exhibits circadian rhythm in the suprachiasmatic nucleus (SCN)—the central circadian pacemaker—and other peripheral tissues. Recent studies have shown that the strong circadian rhythmicity of Dec1 in the SCN was abolished by Clock mutation, whereas that in the liver was affected, but not abolished, by Clock mutation. Moreover, feeding conditions affected hepatic Dec1 expression, which indicates that Dec1 expression is closely linked with the metabolic functions of the liver. Among ligand‐activated nuclear receptors examined, LXRα and LXRβ with T0901317—agonist for LXR—were found to be potent enhancers for Dec1 promoter activity, and a higher expression level of LXRα protein was detected in the liver than in the kidney and heart. T0901317 increased the levels of endogenous Dec1 transcript in hepatoma cells. Chromatin immunoprecipitation assay indicated that LXRα bound to the Dec1 promoter, and an LXRα‐binding site was identified. These observations indicate that hepatic DEC1 mediates the ligand‐dependent LXR signal to regulate the expression of genes involved in the hepatic clock system and metabolism.