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• W2132742407 abstract "Serotonin (5-HT) transporter (5-HTT) plays a key role in the control of 5-HT neuronal activity by reuptaking extracellular 5-HT from the synapse cleft. We have previously demonstrated that <i>5-HTT</i> mRNA expression levels and its uptake activity in the mouse midbrain are significantly higher in the dark phase than those in the light phase. However, the molecular mechanisms of time-dependent expression of <i>5-HTT</i> have not been clarified. In this study, expression of <i>5-HTT</i> mRNA in the mouse midbrain showed a significant 24-h rhythm and was higher in the dark phase. Although such an oscillation was eliminated by a <i>Clock</i> gene mutation, CLOCK and BMAL1 did not activate <i>5-HTT</i> transcription in the luciferase reporter assay. Activating transcription factor-4 (ATF4), a member of the ATF/cAMP response element (CRE)-binding protein family, is a component responsible for sustaining circadian oscillations of CRE-mediated gene expression. ATF4 significantly activated <i>5-HTT</i> transcription in vitro and time dependently bound to the CRE site in the <i>5-HTT</i> promoter in the mouse midbrain. In addition, mutation of the <i>Clock</i> gene disrupted temporal binding of ATF4 to the CRE site in the <i>5-HTT</i> promoter. These results indicated that the circuit of circadian-basis molecular regulation between the clockwork system and mouse <i>5-HTT</i> gene was connected by the ATF4 signaling pathway." @default.
• W2132742407 created "2016-06-24" @default.
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• W2132742407 date "2012-05-09" @default.
• W2132742407 modified "2023-10-18" @default.
• W2132742407 title "Role of Activating Transcription Factor-4 in 24-Hour Rhythm of Serotonin Transporter Expression in the Mouse Midbrain" @default.
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• W2132742407 doi "https://doi.org/10.1124/mol.112.079079" @default.
• W2132742407 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22572884" @default.
• W2132742407 hasPublicationYear "2012" @default.
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