Expression of human β-defensin 1 is regulated via c-Myc and the biological clock

Sherman, Hadas; Froy, Oren

doi:10.1016/j.molimm.2008.03.004

Cited by 43 publications

(31 citation statements)

References 34 publications

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“…Both Odc1 and Srm are activated by c-Myc/MAX complexes binding to Eboxes in their regulatory regions (33, 34)-the same binding-site sequence used by BMAL1/CLOCK. It is known that BMAL1/ CLOCK and c-Myc can regulate the same genes (35). Also, in MMH-D3 hepatocytes, Odc1 and Srm transcripts peak at a similar time to the known BMAL1/CLOCK targets: Dbp, Per2, and Rorc.…”

Section: Discussionmentioning

confidence: 90%

Cell-autonomous circadian clock of hepatocytes drives rhythms in transcription and polyamine synthesis

Atwood

DeConde²,

Wang

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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The circadian clock generates daily rhythms in mammalian liver processes, such as glucose and lipid homeostasis, xenobiotic metabolism, and regeneration. The mechanisms governing these rhythms are not well understood, particularly the distinct contributions of the cell-autonomous clock and central pacemaker to rhythmic liver physiology. Through microarray expression profiling in Met murine hepatocytes (MMH)-D3, we identified over 1,000 transcripts that exhibit circadian oscillations, demonstrating that the cell-autonomous clock can drive many rhythms, and that MMH-D3 is a valid circadian model system. The genes represented by these circadian transcripts displayed both cophasic and antiphasic organization within a protein-protein interaction network, suggesting the existence of competition for binding sites or partners by genes of disparate transcriptional phases. Multiple pathways displayed enrichment in MMH-D3 circadian transcripts, including the polyamine synthesis module of the glutathione metabolic pathway. The polyamine synthesis module, which is highly associated with cell proliferation and whose products are required for initiation of liver regeneration, includes enzymes whose transcripts exhibit circadian oscillations, such as ornithine decarboxylase and spermidine synthase. Metabolic profiling revealed that the enzymatic product of spermidine synthase, spermidine, cycles as well. Thus, the cell-autonomous hepatocyte clock can drive a significant amount of transcriptional rhythms and orchestrate physiologically relevant modules such as polyamine synthesis.networks | chronobiology | resistance distance M any aspects of mammalian physiology and behavior display circadian (∼24-h) rhythms, including the sleep/wake cycle, blood pressure, heart rate, metabolism, and liver regeneration (1, 2). These rhythms are regulated by the circadian clock, which enables consolidation and coordination of physiological events to specific phases of the 24-h cycle in anticipation of daily environmental changes. Dysfunction of the clock is associated with serious human health conditions, including shift work syndrome, sleep disorders, increased risk of cancer, cardiovascular disease, and metabolic syndrome (1, 2).The circadian clock is a self-sustaining, entrainable, cell-autonomous network of three interlocked transcriptional negative feedback loops (2). The primary loop consists of BMAL1/CLOCK transcriptional activators, which dimerize and turn on transcription of Period (Per1, Per2, and Per3) and Crytochrome (Cry1 and Cry2) genes through E-box elements. PER and CRY proteins dimerize and feed back to inhibit BMAL1/CLOCK activation. Two associate loops interlock with the core loop: the ROR/REV-ERB element (RRE) loop composed of ROR activators (RORa, RORb, and RORc) and REV-ERB repressors (REV-ERBα and REV-ERBβ), which compete for RRE transcription factor binding sites (TFBS), and the D-box loop composed of the activator DBP and repressor E4BP4, which act through D-box TFBS (2).In addition to internal regulation of clock genes,...

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Section: Discussionmentioning

confidence: 90%

Cell-autonomous circadian clock of hepatocytes drives rhythms in transcription and polyamine synthesis

Atwood

DeConde²,

Wang

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…In this regard, it is intriguing that the Clock-Bmal1 heterodimer, the positive loop of the circadian clock, binds to E-box and E-box-like enhancer sequences to mediate the transcription of certain genes in cooperation with Myc family proteins (24,25). Nevertheless, the association of hnRNP U with the c-Myc-Max complex is essential for ODC gene induction by growth stimulation (Fig.…”

Section: Discussionmentioning

confidence: 99%

hnRNP U interacts with the c-Myc-Max complex on the E-box promoter region inducing the ornithine decarboxylase gene

Matsuoka¹

2009

Oncol Rep

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Abstract. The promoter of the ornithine decarboxylase (ODC) gene contains two E-boxes, which are critical sites for transcriptional activation by the binding of c-Myc-Max heterodimers. We have identified heterogeneous nuclear ribonuclear protein U (hnRNP U) as a component of the complex formed on the E-box-containing promoter region of the ODC gene by using DNA-affinity chromatography, immunoprecipitation and chromatin immunoprecipitation assays. The N-terminal domain of hnRNP U was responsible for the association with c-Myc-Max complex. Down-regulation of hnRNP U with RNA interference blocked the induction of the ODC gene and cell growth by serum stimulation, suggesting that hnRNP U is a coactivator of the c-Myc-Max complex and essential for cell proliferation. Electrophoretic mobility-shift assays revealed that the segment between the two E-boxes in the promoter is the primary binding site of hnRNP U. The putative binding sequence was narroweddown to a 13-nucleotide segment by comparing the sequence between the E-boxes with the binding sites of hnRNP U, which were recently identified in the promoter of Bmal1, a core component of the circadian molecular oscillator. These findings increase our knowledge of how the c-Myc-Max complex exerts its transcriptional regulatory role and suggest that hnRNP U may be a coactivator of this transcriptional activator complex.

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“…HCT116 cells contain a functional circadian clock, and seliciclib is a CDK inhibitor currently under development, which has previously been shown to display a chronotoxicity profile in mice. 24,25 Results obtained with 2 different siRNAs per target indicate that silencing of the mitotic and anti-apoptotic gene Birc5 (also known as survivin) most efficiently and consistently led to an increased sensitivity of HCT116 cells to the seliciclib treatment (Fig. 3A).…”

Section: Birc5 Expression Modulates Colon Cells Sensitivity To the CDmentioning

confidence: 99%

Functional genomics identifyBirc5/Survivinas a candidate gene involved in the chronotoxicity of cyclin-dependent kinase inhibitors

Siffroi-Fernandez

Dulong

et al. 2014

Cell Cycle

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Expression of human β-defensin 1 is regulated via c-Myc and the biological clock

Cited by 43 publications

References 34 publications

Cell-autonomous circadian clock of hepatocytes drives rhythms in transcription and polyamine synthesis

Cell-autonomous circadian clock of hepatocytes drives rhythms in transcription and polyamine synthesis

hnRNP U interacts with the c-Myc-Max complex on the E-box promoter region inducing the ornithine decarboxylase gene

Functional genomics identifyBirc5/Survivinas a candidate gene involved in the chronotoxicity of cyclin-dependent kinase inhibitors

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