Cellular signal transduction is governed by multiple feedback mechanisms to elicit robust cellular decisions. We combined mathematical modeling and extensive time-resolved data sets in primary erythroid progenitor cells and dissected the roles of the two transcriptional feedback regulators of the SOCS family, CIS and SOCS3 in JAK2/STAT5 signaling. Our model revealed that both feedbacks are most effective at different ligand concentration ranges.
Division of labor by dual feedback regulators controls JAK2/STAT5 signaling over broad ligand range.
Specimen part
View SamplesThe Hippocampus Consortium data set provides estimates of mRNA expression in the adult hippocampus of 99 genetically diverse strains of mice including 67 BXD recombinant inbred strains, 13 CXB recombinant inbred strains, a diverse set of common inbred strains, and two reciprocal F1 hybrids.
Genetics of the hippocampal transcriptome in mouse: a systematic survey and online neurogenomics resource.
Sex, Age, Specimen part
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Dynamic changes in 5-hydroxymethylation signatures underpin early and late events in drug exposed liver.
Sex, Specimen part, Treatment, Time
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Homer1a is a core brain molecular correlate of sleep loss.
No sample metadata fields
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STAT6 transcription factor is a facilitator of the nuclear receptor PPARγ-regulated gene expression in macrophages and dendritic cells.
Specimen part, Treatment, Subject, Time
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Conserved principles of mammalian transcriptional regulation revealed by RNA half-life.
No sample metadata fields
View SamplesCopy number variation (CNV) of DNA segments has recently been identified as a major source of genetic diversity, but a more comprehensive understanding of the extent and phenotypic effect of this type of variation is only beginning to emerge. In this study we generated genome-wide expression data from 6 mouse tissues to investigate how CNVs influence gene expression.
Segmental copy number variation shapes tissue transcriptomes.
No sample metadata fields
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Zebrafish Pou5f1-dependent transcriptional networks in temporal control of early development.
No sample metadata fields
View SamplesMethylazoxymethanol (MAM), the genotoxic metabolite of the cycad azoxyglucoside cycasin, induces genetic alterations in bacteria, yeast, plants, insects and mammalian cells, but adult nerve cells are thought to be unaffected. We show that the brains of young adult mice treated with a single systemic dose of MAM display DNA damage (O6-methylguanine lesions) that peaks at 48 hours and decline to near-normal levels at 7 days post-treatment. By contrast, at this time, MAM-treated mice lacking the gene encoding the DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT), showed persistent O6-methylguanine DNA damage. The DNA damage was linked to cell-signaling pathways that are perturbed in cancer and neurodegenerative disease. These data are consistent with the established carcinogenic and developmental neurotoxic properties of MAM in rodents, and they support the proposal that cancer and neurodegeneration share common signal transduction pathways. They also strengthen the hypothesis that early life exposure to the MAM glucoside cycasin has an etiological association with a declining, prototypical neurodegenerative disease seen in Guam, Japan, and New Guinea populations that formerly used the neurotoxic cycad plant for medicine and/or food. Exposure to environmental genotoxins may have relevance to the etiology of related tauopathies, notably, Alzheimers disease, as well as cancer.
The cycad genotoxin MAM modulates brain cellular pathways involved in neurodegenerative disease and cancer in a DNA damage-linked manner.
Sex, Specimen part, Time
View SamplesThese studies address temporal changes in gene expression during spontaneous sleep and extended wakefulness in the mouse cerebral cortex, a neuronal target for processes that control sleep; and the hypothalamus, an important site of sleep regulatory processes. We determined these changes by comparing expression in sleeping animals sacrificed at different times during the lights on period, to that in animals sleep deprived and sacrificed at the same diurnal time.
Macromolecule biosynthesis: a key function of sleep.
Sex, Age, Specimen part
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