Liver X receptors (LXRalpha and LXRbeta) are potent regulators for hepatic Dec1 expression.
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, LXRalpha and LXRbeta with T0901317-agonist for LXR-were found to be potent enhancers for Dec1 promoter activity, and a higher expression level of LXRalpha 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 LXRalpha bound to the Dec1 promoter, and an LXRalpha-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.
Noshiro
Mitsuhide
M
Department of Dental and Medical Biochemistry, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima 734-8553, Japan. noshiro@hiroshima-u.ac.jp
Usui
Emiko
E
Kawamoto
Takeshi
T
Sato
Fuyuki
F
Nakashima
Ayumu
A
Ueshima
Taichi
T
Honda
Kiyomasa
K
Fujimoto
Katsumi
K
Honma
Sato
S
Honma
Ken-ichi
K
Makishima
Makoto
M
Kato
Yukio
Y
D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D056926:CLOCK Proteins; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D000071518:Liver X Receptors; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D009928:Organ Specificity / Q000235:genetics; D057093:Orphan Nuclear Receptors; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics; D015534:Trans-Activators / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators; C491539:Bhlhe40 protein, mouse; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; C538943:CLOCK protein, human; C538944:Clock protein, mouse