The first described feedback loop of the Arabidopsis circadian clock is based on reciprocal regulation between TOC1 and CCA1/LHY. CCA1 and LHY are MYB transcription factors that bind directly to the TOC1 promoter to negatively regulate its expression. Conversely, the activity of TOC1 has remained less well characterized. Genetic data supports that TOC1 is necessary for the reactivation of CCA1/LHY, but there is little description of its biochemical function. Here we show that TOC1 occupies specific genomic regions in the CCA1 and LHY promoters. Purified TOC1 binds directly to DNA through its CCT domain, which is similar to known DNA binding domains. Chemical induction and transient overexpression of TOC1 in Arabidopsis seedlings cause repression of CCA1/LHY expression demonstrating that TOC1 can repress direct targets, and mutation or deletion of the CCT domain prevents this repression showing that DNA binding is necessary for TOC1 action. Furthermore, we use the Gal4/UAS system in Arabidopsis to show that TOC1 acts as a general transcriptional repressor, and that repression activity is in the Pseudoreceiver (PR) domain of the protein. To identify the genes regulated by TOC1 on a genomic scale, we couple TOC1 chemical induction with microarray analysis and identify new potential TOC1 targets and output pathways. Together these results define the biochemical action of the core clock protein TOC1 and refine our perspective on how plant clocks function.
Arabidopsis circadian clock protein, TOC1, is a DNA-binding transcription factor.
No sample metadata fields
View SamplesContinuous regeneration of digestive enzyme (zymogen) secreting chief cells is a normal aspect of stomach function that is disrupted in pre-cancerous lesions. Regulation of zymogenic cell (ZC) differentiation is poorly understood. Here we profile Parietal, Pit, and Zymogenic cells for comparison and study.
The maturation of mucus-secreting gastric epithelial progenitors into digestive-enzyme secreting zymogenic cells requires Mist1.
Specimen part
View SamplesAnalysis of genes regulated by STC1 down-regulation in mouse 4T1 derived clone, 4T1ch9. STC1 expression is associated with tumor growth and metastasis. This study looks at genes affected when STC1 expression is down-regulated by STC1 shRNA.
STC1 expression is associated with tumor growth and metastasis in breast cancer.
Cell line
View SamplesNormal primary thyroid cells were incubated with vehicle, 100 IU/ml IFN-gamma, 50 IU/ml IL1-beta, or a combination of both IFN-gamma and IL1-beta for 24 or 72 hours. The experiment was repeated 5 times using thyroid cells from 5 different patients. RNA expression was analyzed using Affymetrix HG_U133A arrays for 3 of the thyroids, and HG_U133A_2.0 (small version of HG_U133A) arrays for 2 of the thyroids.
Microarray analysis of cytokine activation of apoptosis pathways in the thyroid.
No sample metadata fields
View SamplesMolecular mechanisms that regulate the generation of hematopoietic and endothelial cells from mesoderm are poorly understood.
GATA2 functions at multiple steps in hemangioblast development and differentiation.
No sample metadata fields
View SamplesHuman samples of 33 adrenocortical carcinomas, 22 adrenocortical adenomas, and 10 normal adrenal cortex samples, each from a different patient, had mRNA assays performed using Affymetrix HG_U133_plus_2 arrays, with 54675 probe-sets. We note that the same array data is in GEO series GSE33371, where we assayed the cancer samples for Beta-catenin staining or mutation, and make new comparisons based on those assays.
Molecular classification and prognostication of adrenocortical tumors by transcriptome profiling.
Sex, Age
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Tristetraprolin impairs myc-induced lymphoma and abolishes the malignant state.
Specimen part
View SamplesSpecific pathogen free wild-type C57Bl/6 male mice fed ketogenic diet (Bio-Serv AIN-76-A) for 4 weeks
Adaptation of myocardial substrate metabolism to a ketogenic nutrient environment.
Sex, Specimen part
View SamplesMyc oncoproteins directly regulate transcription by binding to target genes, yet this only explains a fraction of the genes affected by Myc. mRNA turnover is controlled via AU-binding proteins (AUBPs) that recognize AU-rich elements (AREs) found within many transcripts. Analyses of precancerous and malignant Myc-expressing B cells revealed that Myc regulates hundreds of ARE-containing (ARED) genes and select AUBPs. Notably, Myc directly suppresses transcription of Tristetraprolin (TTP/ZFP36), an mRNA-destabilizing AUBP, and this circuit is also operational during B lymphopoiesis and IL7 signaling. Importantly, TTP suppression is a hallmark of cancers with MYC involvement, and restoring TTP impairs Myc-induced lymphomagenesis and abolishes maintenance of the malignant state. Further, there is a selection for TTP loss in malignancy; thus, TTP functions as a tumor suppressor. Finally, Myc/TTP-directed control of select cancer-associated ARED genes is disabled during lymphomagenesis. Thus, Myc targets AUBPs to regulate ARED genes that control tumorigenesis.
Tristetraprolin impairs myc-induced lymphoma and abolishes the malignant state.
Specimen part
View SamplesMyc oncoproteins directly regulate transcription by binding to target genes, yet this only explains a fraction of the genes affected by Myc. mRNA turnover is controlled via AU-binding proteins (AUBPs) that recognize AU-rich elements (AREs) found within many transcripts. Analyses of precancerous and malignant Myc-expressing B cells revealed that Myc regulates hundreds of ARE-containing (ARED) genes and select AUBPs. Notably, Myc directly suppresses transcription of Tristetraprolin (TTP/ZFP36), an mRNA-destabilizing AUBP, and this circuit is also operational during B lymphopoiesis and IL7 signaling. Importantly, TTP suppression is a hallmark of cancers with MYC involvement, and restoring TTP impairs Myc-induced lymphomagenesis and abolishes maintenance of the malignant state. Further, there is a selection for TTP loss in malignancy; thus, TTP functions as a tumor suppressor. Finally, Myc/TTP-directed control of select cancer-associated ARED genes is disabled during lymphomagenesis. Thus, Myc targets AUBPs to regulate ARED genes that control tumorigenesis.
Tristetraprolin impairs myc-induced lymphoma and abolishes the malignant state.
Specimen part
View Samples