The circadian PAR-domain basic leucine zipper transcription factors DBP, TEF, and HLF modulate basal and inducible xenobiotic detoxification

Gachon, Frédéric; Olela, Fabienne Fleury; Schaad, Olivier; Descombes, Patrick; Schibler, Ulrich

doi:10.1016/j.cmet.2006.04.015

Cited by 461 publications

(457 citation statements)

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“…The figure shows a representative experiment with four probes that cover a region from À197 to À113 and includes the only sequence that binds TEF as determined by using anti-FLAG antibodies sion of many enzymes and regulators involved in detoxification and drug metabolism. 5 However, the relevance of PAR bZIP proteins at the cellular level has not been thoroughly investigated. By using mouse tail fibroblasts from PAR bZIP (À/À) mice, we showed that PAR bZIP proteins, mainly TEF, were needed to maintain the basal mRNA levels of bik, a BH3-only proapoptotic member of the Bcl-2 family.…”

Section: Discussionmentioning

confidence: 99%

“…4 These proteins have recently been shown to control the expression of many enzymes and regulators involved in detoxification and drug metabolism, such as cytochrome P450 enzymes, carboxylesterases, and constitutive androstane receptor. 5 In addition, we showed for the first time that PAR bZIP proteins regulate the expression of a gene, bcl-gS, involved in the execution of apoptosis. This transcriptional pathway can be activated by chemotherapeutic agents in cancer cells, thus contributing to the apoptotic response to chemotherapy.…”

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confidence: 99%

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PAR bZIP-bik is a novel transcriptional pathway that mediates oxidative stress-induced apoptosis in fibroblasts

2009

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PAR bZIP (cells knockout for PAR bZIP transcription factors) proteins, thyrotroph embryonic factor (TEF), albumin D-site-binding protein (DBP), and hepatic leukemia factor (HLF), are a family of transcription factors that have been shown to contribute to the expression of genes involved in detoxification and drug metabolism. Recently, we showed that PAR bZIP proteins were able to regulate the BH3-only gene bcl-gS in tumor cells. Here, we have extended the role of these transcription factors in the control of apoptosis executors by analyzing the expression of BH3-only genes in PAR bZIP triple knockout mouse fibroblasts. We found that bik was the only BH3-only gene downregulated in knockout cells. Consistently, transfection of TEF or DBP induces the expression of endogenous bik, regardless of the presence of active p53. Moreover, both promoter-reporter and chromatin immunoprecipitation assays indicate that PAR bZIP proteins activate the bik promoter directly. Treatment with different stress stimuli reveals a higher survival of knockout fibroblasts compared with that of wild-type cells, especially after incubation with H 2 O 2 , which suggest that PAR bZIP proteins participate in oxidative stress-induced apoptosis. Furthermore, the apoptotic cell death promoted by treatment with H 2 O 2 can be impaired by reducing the expression of Bik in wild-type fibroblasts or enhanced by the overexpression of Bik in knockout cells. These findings reveal a novel transcriptional pathway relevant in transducing the apoptotic response to oxidative stress.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

PAR bZIP-bik is a novel transcriptional pathway that mediates oxidative stress-induced apoptosis in fibroblasts

2009

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“…In their study, Stratmann et al (2010) have identified a special function of a BMAL1 binding site in the promoter region of the Dbp gene to adjust the phase of its expression according to the photoperiod. Since DBP and the related factors TEF and HLF regulate a variety of metabolic and detoxification enzymes prior to the food uptake of the animals (Gachon et al, 2006), this may be the rationale for this sophisticated regulation. The uncoupling mechanism provides flexibility to the phase of Dbp expression to ascertain that the DBP protein can activate the transcription of the metabolic and detoxification enzymes always prior to the food uptake of the organism.…”

Section: Transcriptional Network Of the Hepatic Circadian Oscillatormentioning

confidence: 99%

“…Interestingly, some factors involved in detoxification share both kinds of regulation. The xenobiotic compound sensor constitutive androstane receptor (CAR; NR1I3) is expressed in a circadian fashion in the liver (Gachon et al, 2006). However, in the presence of xenobiotic ligands, its expression is super-induced.…”

Section: Introductionmentioning

confidence: 99%

The role of clock genes and rhythmicity in the liver

Schmutz

Albrecht

Ripperger

2012

Molecular and Cellular Endocrinology

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The liver is the important organ to maintain energy homeostasis of an organism. To achieve this, many biochemical reactions run in this organ in a rhythmic fashion. An elegant way to coordinate the temporal expression of genes for metabolic enzymes relies in the link to the circadian timing system. In this fashion not only a maximum of synchronization is achieved, but also anticipation of daily recurring events is possible. Here we will focus on the input and output pathways of the hepatic circadian oscillator and discuss the recently found flexibility of its circadian transcriptional networks.

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“…In particular, hepatic lipogenesis, gluconeogenesis, heme, and bile acid biosynthesis as well as xenobiotic detoxification are cyclic in rodents and humans. [10][11][12][13] In contrast, some key regulators in circadian clock have their own metabolic functions. For example, RORa, activator of Bmal1, can regulate lipid flux, lipogenesis, and lipid storage in skeletal muscle.…”

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confidence: 99%

SWItch/sucrose nonfermentable (SWI/SNF) complex subunit BAF60a integrates hepatic circadian clock and energy metabolism

et al. 2011

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Many aspects of energy metabolism, including glucose and lipid homeostasis and mitochondrial oxidative metabolism, are under precise control by the mammalian circadian clock. However, the molecular mechanism for coordinate integration of the circadian clock and various metabolic pathways is poorly understood. Here we show that BAF60a, a chromatin-remodeling complex subunit, is rhythmically expressed in the liver of mice. Mice with liver-specific knockdown of BAF60a show abnormalities in the rhythmic expression pattern of clock and metabolic genes and in the circulating metabolite profile. Consistently, knockdown of BAF60a impairs the oscillation of clock genes in serum-shocked HepG 2 cells. At the molecular level, BAF60a activates Bmal1 and G6Pase transcription by way of the coactivation of retinoid-related orphan receptor alpha (RORa). In addition, BAF60a is present near ROR response elements (RORE) on the proximal Bmal1 and G6Pase promoters and turns the chromatin structure into the active state. Conclusion: Our data suggest a critical role for BAF60a in the coordinated regulation of hepatic circadian clock and energy metabolism in mammals. (HEPATOLOGY 2011;54:1410-1420 M any physiological events in mammals, including locomotor activity, sleep, blood pressure, circulating hormones, and energy metabolism show diurnal fluctuation. 1,2 These intrinsic biological rhythms are mainly entrained by light-dark (LD) and feeding cycles. The mammalian master clock resides in the hypothalamic suprachiasmatic nucleus (SCN) and drives slave oscillators distributed in various peripheral tissues through behavioral and neuroendocrine signals. However, Damiola et al. 3 found that peripheral oscillators can be uncoupled and reset from the central pacemaker by restricted feeding. Their findings are supported by the subsequent report showing that restricted feeding entrains the circadian rhythms in peripheral tissues, dominantly in the liver, but leaving SCN rhythms unaffected. 4 Also, both food availability and the temporal pattern of feeding determine the repertoire, phase, and amplitude of the circadian transcriptome in mouse liver. 5 All these studies indicate that nutritional signals play a dominant role in the regulation of peripheral clock function. At the molecular level, Clock and Bmal1 are two basic helix-loop-helix transcription factors that activate the transcription of period (Per) and cryptochrome (Cry) genes. 6 Per and Cry proteins in turn inhibit their own expression by repressing Clock/Bmal1 activity, forming the critical feedback loop within the clock circuitry. In addition, the orphan nuclear receptors of the ROR and Rev-erb families are also implicated in the control of circadian clock function. 7,8 Abbreviations: ChIP, chromatin immunoprecipitation; CO, carbon monoxide; CoIP, coimmunoprecipitation; GFP, green fluorescent protein; GR, glucocorticoid receptor; H3K4me3, trimethylation of lysine 4 of histone 3; H3K9me2, dimethylation of lysine 9 of histone 3; HAT, histone acetyltransferase; HDAC, histone deacetyla...

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The circadian PAR-domain basic leucine zipper transcription factors DBP, TEF, and HLF modulate basal and inducible xenobiotic detoxification

Cited by 461 publications

References 45 publications

PAR bZIP-bik is a novel transcriptional pathway that mediates oxidative stress-induced apoptosis in fibroblasts

PAR bZIP-bik is a novel transcriptional pathway that mediates oxidative stress-induced apoptosis in fibroblasts

The role of clock genes and rhythmicity in the liver

SWItch/sucrose nonfermentable (SWI/SNF) complex subunit BAF60a integrates hepatic circadian clock and energy metabolism

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