Dec1 and Dec2 Expression is Disrupted in the Suprachiasmatic Nuclei of Clock Mutant Mice

Butler, Matthew; Honma, Sato; Fukumoto, Tatsuya; Kawamoto, Takeshi; Fujimoto, Katsumi; Noshiro, Mitsuhide; Kato, Yukio; Honma, K.

doi:10.1177/0748730403262870

Cited by 29 publications

(28 citation statements)

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“…Previously, we reported high expression levels of Dec1 and Per1 at ZT 2, soon after lights-on, in the extra SCN brain tissues (Butler et al, 2004). In the present experiment, we also observed increased gene expression, which suggested the positive masking of light (Dec1 and Dec2 in the liver and kidney).…”

Section: Discussionsupporting

confidence: 79%

“…Mutant CLOCK protein lacks 51-amino acids because of the deletion of exon 19 and becomes inactive (Gekakis et al, 1998;King et al, 1997). The expression profiles of all clock genes are disrupted with reduced peak expression in the SCN of Clock/Clock mice Kume et al, 1999;Oishi et al, 2000), and we recently reported that the expression of Dec1 and Dec2 in the SCN is also disrupted (Butler et al, 2004). These findings suggest that CLOCK activates Dec1 and Dec2 transcription in vivo.…”

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confidence: 90%

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Tissue-Specific Disruption of Rhythmic Expression of Dec1 and Dec2 in Clock Mutant Mice

et al. 2005

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DEC1 and DEC2-basic helix-loop-helix transcription factors-exhibit a circadian expression in the suprachiasmatic nucleus and other peripheral tissues and seem to play roles in regulating the mammalian circadian rhythm by suppressing the CLOCK/BMAL1-activated promoters of Per1, Dec1, and Dec2. The authors present data on the expression patterns of mRNA for Dec1, Dec2, Per2, Dbp, and Npas2 in various tissues of wild-type and homozygous Clock mutant mice (Clock/Clock). The Clock mutation resulted in extreme reduction of Dec1 expression in kidney, heart, and skeletal muscle but not in liver, whereas it strongly repressed Dec2 expression in liver, kidney, and heart, while Dec2 expression in skeletal muscle remained rhythmic. Per2 also showed the tissue-dependent disruption of the rhythmicity by Clock mutation, whereas rhythmic expression of Dbp in Clock mutant mice disappeared in all tissues examined. Npas2, a structurally and functionally related gene to Clock, showed significant levels of expression in the liver and kidney with a robust rhythmicity, which was also affected by Clock mutation. These marked changes in the Dec1 and Dec2 expression, as well as in the Per2, Dbp, and Npas2 expression in the periphery by Clock mutation, indicated that CLOCK plays a major role in the expression of these genes in most tissues. However, circadian expression of Dec1 in liver and kidney and that of Dec2 in skeletal muscle of Clock mutant mice suggested that CLOCK-independent circadian regulation operates in some tissues.

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confidence: 79%

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Tissue-Specific Disruption of Rhythmic Expression of Dec1 and Dec2 in Clock Mutant Mice

et al. 2005

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“…and rhythmic expression of Dec2 in the kidney of rats under a normal LD cycle. This differs not only from the circadian expression of Dec1 and Dec2 in the heart (present study) and in the SCN (Butler et al, 2004;Honma et al, 2002) and other peripheral tissues (Kawamoto et al, 2006;Kawamoto et al, 2004;Wu et al, 2008a;Wu et al, 2008b) of rats and mice but also from observations in mouse kidney (Hamaguchi et al, 2004;Noshiro et al, 2005), which suggests tissue-and species-specific mechanisms underlying the circadian expression of these two clock genes. This unusual phenomenon may be the cause of overlapping functions of Dec1 and Dec2 in maintaining and entraining circadian rhythms.…”

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confidence: 48%

Significant dissociation of expression patterns of the basic helix–loop–helix transcription factors Dec1 and Dec2 in rat kidney

Ota

Zhuge

et al. 2011

Journal of Experimental Biology

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SUMMARYDec1 and Dec2 are regulators of the mammalian molecular clock that show robust circadian rhythms in the suprachiasmatic nucleus and various peripheral tissues. Although the expression of Dec1 and Dec2 is altered by multiple stimuli in different organs, their transcriptional regulatory mechanisms have not been fully elucidated for the kidney. In the present study, we describe for the first time significant dissociation of expression patterns with arrhythmic expression of Dec1 and rhythmic expression of Dec2 in rat kidney under a normal light-dark (LD) cycle. Daytime restricted feeding (RF) significantly altered the expression patterns of these two clock genes, and even induced circadian expression of Dec1 with an amplitude of 2.2 on day3 and 4.2 on day7. However, when a reversed feeding schedule was coupled with a reversed LD cycle, the expression of Dec1 but not Dec2 reverted to being arrhythmic. Moreover, exogenous injection of the glucocorticoid analogue dexamethasone (Dex) at certain times of the day resulted in rhythmic expression of Dec1, which was similar to that seen following RF for 7days. In contrast, endogenous disruption of glucocorticoids by adrenalectomy abolished RF-induced rhythmic expression of Dec1 in the kidney. These observations suggest the existence of a glucocorticoid gating mechanism in the circadian expression of Dec1 in rat kidney. Supplementary material available online at

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“…Among suppressive factors for E boxes, DEC1 and DEC2 can bind directly to E boxes through their basic helix-loop-helix DNA binding domains (18,26), although it remains unclear whether DEC1 and DEC2 also bind to the EЈ boxes. In contrast, PER and CRY interact with the CLOCK/BMAL1 heterodimer but cannot bind directly to E/EЈ boxes, since they have no DNA binding domain.Dec1 expression shows robust circadian rhythms in the suprachiasmatic nucleus and various peripheral tissues (7,10,14,17,18,23), and it is further enhanced by light pulse, hypoxia, or growth factors, with the Dec1 level gradually increasing during chondrogenic or osteogenic differentiation (6,14,15,22,25,(27)(28)(29). Dec1 expression can also be elevated in various tissues by refeeding after starvation (17).…”

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DEC1 Modulates the Circadian Phase of Clock Gene Expression

Nakashima¹,

Kawamoto²,

Honda

et al. 2008

Molecular and Cellular Biology

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DEC1 suppresses CLOCK/BMAL1-enhanced promoter activity, but its role in the circadian system of mammals remains unclear. Here we examined the effect of Dec1 overexpression or deficiency on circadian gene expression triggered with 50% serum. Overexpression of Dec1 delayed the phase of clock genes such as Dec1, Dec2, Per1, and Dbp that contain E boxes in their regulatory regions, whereas it had little effect on the circadian phase of Per2 and Cry1 carrying CACGTT E boxes. In contrast, Dec1 deficiency advanced the phase of the E-box-containing clock genes but not that of the E-box-containing clock genes. Accordingly, DEC1 showed strong binding and transrepression on the E box, but not on the E box, in chromatin immunoprecipitation, electrophoretic mobility shift, and luciferase reporter assays. Dec1 ؊/؊ mice showed behavioral rhythms with slightly but significantly longer circadian periods under conditions of constant darkness and faster reentrainment to a 6-h phase-advanced shift of a light-dark cycle. Knockdown of Dec2 with small interfering RNA advanced the phase of Dec1 and Dbp expression, and double knockdown of Dec1 and Dec2 had much stronger effects on the expression of the E-box-containing clock genes. These findings suggest that DEC1, along with DEC2, plays a role in the finer regulation and robustness of the molecular clock.The mammalian molecular clock system consists of various clock genes and their protein products involved in interlocked feedback loops of transcriptional and translational regulation through clock elements such as CACGTG E-box, D-box, and ROR/REV-ERB binding elements (RORE) (18,24). Among these regulatory sequences, the E box is thought to be the most important element in the molecular oscillatory system, since it is the binding site for the CLOCK/BMAL1 heterodimer, which up-regulates various clock genes, including Dec1, Dec2, Per1, Dbp, and Rev-erb␣. In this regulatory system, PER, CRY, and DEC serve as negative factors for transcription from E-boxdriven promoters, and the E-box-like element EЈ box (CAC GTT) was recently shown to be involved in the direct regulation of Per2 and Cry1 genes by CLOCK/BMAL1 (1, 31, 34). RORE, on the other hand, is a clock element to which the transcriptional activators-ROR␣/ROR␤/ROR␥-and repressors-REV-ERB␣/REV-ERB␤-bind, and ROR and REV-ERB regulate the circadian expression of Bmal1, Clock, Npas2, and Cry1 via RORE (31).In the mammalian clock system, DEC1 (also known as BHLHB2, STRA13, or SHARP2) and DEC2 (BHLHB3 or SHARP1) serve as transcriptional repressors for CLOCK/ BMAL1-enhanced promoter activity, through binding to E boxes or interaction with BMAL1 (12,14,18,26). Among suppressive factors for E boxes, DEC1 and DEC2 can bind directly to E boxes through their basic helix-loop-helix DNA binding domains (18,26), although it remains unclear whether DEC1 and DEC2 also bind to the EЈ boxes. In contrast, PER and CRY interact with the CLOCK/BMAL1 heterodimer but cannot bind directly to E/EЈ boxes, since they have no DNA binding domain.Dec1 expression shows...

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Dec1 and Dec2 Expression is Disrupted in the Suprachiasmatic Nuclei of Clock Mutant Mice

Cited by 29 publications

References 28 publications

Tissue-Specific Disruption of Rhythmic Expression of Dec1 and Dec2 in Clock Mutant Mice

Tissue-Specific Disruption of Rhythmic Expression of Dec1 and Dec2 in Clock Mutant Mice

Significant dissociation of expression patterns of the basic helix–loop–helix transcription factors Dec1 and Dec2 in rat kidney

DEC1 Modulates the Circadian Phase of Clock Gene Expression

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