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ABSTRACT:
PROVIDER: PRJNA177596 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Circadian rhythms are responsive to a variety of external cues, light and metabolism being the most important. In mammals, the light signal is sensed by the retina and transmitted to the SCN master clock, where it is translated into the molecular oscillator via regulation of clock gene transcription. The signalling pathways governing the molecular translation from metabolic signals to circadian output in peripheral oscillators, in contrast, are less understood. FOXO transcription factors are known to translate external metabolic cues to internal transcriptional programs. In the past couple of years it has become evident that both FOXO transcription factors and the circadian clock are of key importance in the underlying mechanisms of ageing and the regulation of metabolism. We now show FOXO3 to be a crucial modulator of circadian rhythmicity via direct transcriptional regulation of Clock, a core component of the molecular oscillator, and identify FOXO3 as a novel link in the circadian feedback loop, which is required for circadian rhythms in liver. We propose that FOXO3 directly feeds back into the circadian oscillator in response to metabolic cues.
2014-06-03 | GSE41555 | GEO
Project description:Circadian rhythms are responsive to a variety of external cues, light and metabolism being the most important. In mammals, the light signal is sensed by the retina and transmitted to the SCN master clock, where it is translated into the molecular oscillator via regulation of clock gene transcription. The signalling pathways governing the molecular translation from metabolic signals to circadian output in peripheral oscillators, in contrast, are less understood. FOXO transcription factors are known to translate external metabolic cues to internal transcriptional programs. In the past couple of years it has become evident that both FOXO transcription factors and the circadian clock are of key importance in the underlying mechanisms of ageing and the regulation of metabolism. We now show FOXO3 to be a crucial modulator of circadian rhythmicity via direct transcriptional regulation of Clock, a core component of the molecular oscillator, and identify FOXO3 as a novel link in the circadian feedback loop, which is required for circadian rhythms in liver. We propose that FOXO3 directly feeds back into the circadian oscillator in response to metabolic cues.
2014-06-03 | GSE41554 | GEO
Project description:MH003B:FOXO3 in control of circadian rhythms via direct regulation of Clock. Part 2: knockdown of FoxO3.
| PRJNA177601 | ENA
Project description:Circadian rhythms are responsive to a variety of external cues, light and metabolism being the most important. In mammals, the light signal is sensed by the retina and transmitted to the SCN master clock, where it is translated into the molecular oscillator via regulation of clock gene transcription. The signalling pathways governing the molecular translation from metabolic signals to circadian output in peripheral oscillators, in contrast, are less understood. FOXO transcription factors are known to translate external metabolic cues to internal transcriptional programs. In the past couple of years it has become evident that both FOXO transcription factors and the circadian clock are of key importance in the underlying mechanisms of ageing and the regulation of metabolism. We now show FOXO3 to be a crucial modulator of circadian rhythmicity via direct transcriptional regulation of Clock, a core component of the molecular oscillator, and identify FOXO3 as a novel link in the circadian feedback loop, which is required for circadian rhythms in liver. We propose that FOXO3 directly feeds back into the circadian oscillator in response to metabolic cues. We performed a microarray study on synchronized NIH 3T3 cells upon transient knock-down of FoxO3 (siO3). Cells were harvested for RNA isolation 24h (time1), 30h(time2), 36h(time3) and 42h(time4) after synchronization. Experimental samples were hybridized against a reference pool of cRNA, which was derived from unsynchronized NIH 3T3 cells. AS controlgroup a scrambled siRNA was transfected. Experiments were performed 4 times, of each sample group two samples were labeled with cy5 and co-hybridized with reference RNA labeled with cy3, and two samples were labeled and hybridized in the opposite way. Microarrays used were Mouse Whole Genome Gene Expression Microarrays V1 (Agilent Technologies, Belgium)
2014-06-03 | E-GEOD-41555 | biostudies-arrayexpress
Project description:Circadian rhythms are responsive to a variety of external cues, light and metabolism being the most important. In mammals, the light signal is sensed by the retina and transmitted to the SCN master clock, where it is translated into the molecular oscillator via regulation of clock gene transcription. The signalling pathways governing the molecular translation from metabolic signals to circadian output in peripheral oscillators, in contrast, are less understood. FOXO transcription factors are known to translate external metabolic cues to internal transcriptional programs. In the past couple of years it has become evident that both FOXO transcription factors and the circadian clock are of key importance in the underlying mechanisms of ageing and the regulation of metabolism. We now show FOXO3 to be a crucial modulator of circadian rhythmicity via direct transcriptional regulation of Clock, a core component of the molecular oscillator, and identify FOXO3 as a novel link in the circadian feedback loop, which is required for circadian rhythms in liver. We propose that FOXO3 directly feeds back into the circadian oscillator in response to metabolic cues. We performed a microarray study on synchronized NIH 3T3 cells upon transient overexpression of FoxO6 (oeO6). Cells were harvested for RNA isolation 24h (time1), 30h(time2), 36h(time3) and 42h(time4) after synchronization. Experimental samples were hybridized against a reference pool of cRNA, which was derived from unsynchronized NIH 3T3 cells. Experiments were performed 4 times, of each sample group two samples were labeled with cy5 and co-hybridized with reference RNA labeled with cy3, and two samples were labeled and hybridized in the opposite way. Microarrays used were Mouse Whole Genome Gene Expression Microarrays V1 (Agilent Technologies, Belgium)
2014-06-03 | E-GEOD-41554 | biostudies-arrayexpress
Project description:MH003A:FOXO3 in control of circadian rhythms via direct regulation of Clock. Part 1: overexpression of FoxO6
| PRJNA177600 | ENA
Project description:Over the past decade, genome-wide assays have underscored the broad sweep of circadian gene expression. A substantial fraction of the transcriptome undergoes oscillations in many organisms and tissues, which governs the many biochemical, physiological and behavioral functions under circadian control. Based predominantly on the transcription feedback loops important for core circadian timekeeping, it is commonly assumed that this widespread mRNA cycling reflects circadian transcriptional cycling. To address this issue, we directly measured dynamic changes in mouse liver transcription using Nascent-Seq. Many genes are rhythmically transcribed over the 24h day, which include precursors of several non-coding RNAs as well as the expected set of core clock genes. Surprisingly however, nascent RNA rhythms overlap poorly with mRNA abundance rhythms assayed by RNA-seq. This is because most mouse liver genes with rhythmic mRNA expression manifest poor transcriptional rhythms, indicating a prominent role of post-transcriptional regulation in setting mRNA cycling amplitude. To gain further insight into circadian transcriptional regulation, we also characterized the rhythmic transcription of liver genes targeted by the transcription factors CLOCK and BMAL1; they directly target other core clock genes and sit at the top of the molecular circadian clock hierarchy in mammals. CLK:BMAL1 rhythmically bind at the same discrete phase of the circadian cycle to all target genes, which not surprisingly have a much higher percentage of rhythmic transcription than the genome as a whole. However, there is a surprisingly heterogeneous set of cycling transcription phases of direct target genes, which even include core clock genes. This indicates a disconnect between rhythmic DNA binding and the peak of transcription, which is likely due to other transcription factors that collaborate with CLK:BMAL1. In summary, the application of Nascent-Seq to a mammalian tissue provides surprising insights into the rhythmic control of gene expression and should have broad applications beyond the analysis of circadian rhythms. CLK and BMAL1 DNA binding profile in the mouse liver at ZT8, sequenced along an Input sample using GAII (ChIP-Seq) Supplementary file ChIPSeq_Mouse_Liver_Processed_data_Table1.txt represents annotated CLK and BMAL1 peaks.
2012-11-10 | E-GEOD-36874 | biostudies-arrayexpress
Project description:Over the past decade, genome-wide assays have underscored the broad sweep of circadian gene expression. A substantial fraction of the transcriptome undergoes oscillations in many organisms and tissues, which governs the many biochemical, physiological and behavioral functions under circadian control. Based predominantly on the transcription feedback loops important for core circadian timekeeping, it is commonly assumed that this widespread mRNA cycling reflects circadian transcriptional cycling. To address this issue, we directly measured dynamic changes in mouse liver transcription using Nascent-Seq. Many genes are rhythmically transcribed over the 24h day, which include precursors of several non-coding RNAs as well as the expected set of core clock genes. Surprisingly however, nascent RNA rhythms overlap poorly with mRNA abundance rhythms assayed by RNA-seq. This is because most mouse liver genes with rhythmic mRNA expression manifest poor transcriptional rhythms, indicating a prominent role of post-transcriptional regulation in setting mRNA cycling amplitude. To gain further insight into circadian transcriptional regulation, we also characterized the rhythmic transcription of liver genes targeted by the transcription factors CLOCK and BMAL1; they directly target other core clock genes and sit at the top of the molecular circadian clock hierarchy in mammals. CLK:BMAL1 rhythmically bind at the same discrete phase of the circadian cycle to all target genes, which not surprisingly have a much higher percentage of rhythmic transcription than the genome as a whole. However, there is a surprisingly heterogeneous set of cycling transcription phases of direct target genes, which even include core clock genes. This indicates a disconnect between rhythmic DNA binding and the peak of transcription, which is likely due to other transcription factors that collaborate with CLK:BMAL1. In summary, the application of Nascent-Seq to a mammalian tissue provides surprising insights into the rhythmic control of gene expression and should have broad applications beyond the analysis of circadian rhythms.
2012-11-10 | GSE36874 | GEO
Project description:Over the past decade, genome-wide assays have underscored the broad sweep of circadian gene expression. A substantial fraction of the transcriptome undergoes oscillations in many organisms and tissues, which governs the many biochemical, physiological and behavioral functions under circadian control. Based predominantly on the transcription feedback loops important for core circadian timekeeping, it is commonly assumed that this widespread mRNA cycling reflects circadian transcriptional cycling. To address this issue, we directly measured dynamic changes in mouse liver transcription using Nascent-Seq. Many genes are rhythmically transcribed over the 24h day, which include precursors of several non-coding RNAs as well as the expected set of core clock genes. Surprisingly however, nascent RNA rhythms overlap poorly with mRNA abundance rhythms assayed by RNA-seq. This is because most mouse liver genes with rhythmic mRNA expression manifest poor transcriptional rhythms, indicating a prominent role of post-transcriptional regulation in setting mRNA cycling amplitude. To gain further insight into circadian transcriptional regulation, we also characterized the rhythmic transcription of liver genes targeted by the transcription factors CLOCK and BMAL1; they directly target other core clock genes and sit at the top of the molecular circadian clock hierarchy in mammals. CLK:BMAL1 rhythmically bind at the same discrete phase of the circadian cycle to all target genes, which not surprisingly have a much higher percentage of rhythmic transcription than the genome as a whole. However, there is a surprisingly heterogeneous set of cycling transcription phases of direct target genes, which even include core clock genes. This indicates a disconnect between rhythmic DNA binding and the peak of transcription, which is likely due to other transcription factors that collaborate with CLK:BMAL1. In summary, the application of Nascent-Seq to a mammalian tissue provides surprising insights into the rhythmic control of gene expression and should have broad applications beyond the analysis of circadian rhythms.
2012-11-10 | GSE36873 | GEO
Project description:Over the past decade, genome-wide assays have underscored the broad sweep of circadian gene expression. A substantial fraction of the transcriptome undergoes oscillations in many organisms and tissues, which governs the many biochemical, physiological and behavioral functions under circadian control. Based predominantly on the transcription feedback loops important for core circadian timekeeping, it is commonly assumed that this widespread mRNA cycling reflects circadian transcriptional cycling. To address this issue, we directly measured dynamic changes in mouse liver transcription using Nascent-Seq. Many genes are rhythmically transcribed over the 24h day, which include precursors of several non-coding RNAs as well as the expected set of core clock genes. Surprisingly however, nascent RNA rhythms overlap poorly with mRNA abundance rhythms assayed by RNA-seq. This is because most mouse liver genes with rhythmic mRNA expression manifest poor transcriptional rhythms, indicating a prominent role of post-transcriptional regulation in setting mRNA cycling amplitude. To gain further insight into circadian transcriptional regulation, we also characterized the rhythmic transcription of liver genes targeted by the transcription factors CLOCK and BMAL1; they directly target other core clock genes and sit at the top of the molecular circadian clock hierarchy in mammals. CLK:BMAL1 rhythmically bind at the same discrete phase of the circadian cycle to all target genes, which not surprisingly have a much higher percentage of rhythmic transcription than the genome as a whole. However, there is a surprisingly heterogeneous set of cycling transcription phases of direct target genes, which even include core clock genes. This indicates a disconnect between rhythmic DNA binding and the peak of transcription, which is likely due to other transcription factors that collaborate with CLK:BMAL1. In summary, the application of Nascent-Seq to a mammalian tissue provides surprising insights into the rhythmic control of gene expression and should have broad applications beyond the analysis of circadian rhythms.
2012-11-10 | GSE36872 | GEO