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GSE26488
Mus musculus
21 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Abstract of publicaton: CD4/CD8 double-positive (DP) thymocytes express the transcriptional repressor Histone Deacetylase 7 (HDAC7), a class IIa HDAC that is exported from the cell nucleus after T cell receptor (TCR) engagement. Through signal-dependent nuclear export, class IIa HDACs such as HDAC7 mediate signal-dependent changes in gene expression that are important to developmental fate decisions in multiple tissues. We report that HDAC7 is exported from the cell nucleus during positive selection in thymocytes, and regulates genes mediating the coupling between TCR engagement and downstream events that determine cell survival. Thymocytes lacking HDAC7 are inefficiently positively selected due to a severely shortened lifespan and exhibit a truncated repertoire of TCR Jalpha segments. The expression of multiple important mediators and modulators of the response to TCR engagement is altered in HDAC7-deficient thymocytes, resulting in increased tonic MAP kinase activity that contributes to the observed loss of viability. Remarkably, the activity of Protein Kinase D, the kinase that mediates nuclear export of HDAC7 in response to TCR signaling, is also increased in HDAC7-deficient thymocytes, suggesting that HDAC7 nuclear export governs a self-sustaining auto-excitatory loop. These experiments add to the understanding of the life/death decision in thymic T cell development, define a novel function for class IIa HDACs, and point to a novel feed-forward mechanism whereby these molecules regulate their own state and mediate stable developmental transitions. Title of manuscript: Nuclear Export of Histone Deacetylase 7 During Thymic Selection Mediates Immune Self-tolerance. abstract of manuscript: Histone Deacetylase 7 (HDAC7) is a TCR signal-dependent regulator of differentiation that is highly expressed in CD4/CD8 double-positive (DP) thymocytes. Here we examine the effect of blocking TCR-dependent nuclear export of HDAC7 during thymic selection, through expression of a signal-resistant mutant of HDAC7 (HDAC7-?P) in thymocytes. We find that HDAC7-?P Transgenic thymocytes exhibit a profound block in negative thymic selection, but can still undergo positive selection, resulting in the escape of autoreactive T cells into the periphery. Gene expression profiling reveals a comprehensive suppression of the negative selection-associated gene expression program in DP thymocytes, associated with a defect in the activation of MAP kinase pathways by TCR signals. The consequence of this block in vivo is a lethal autoimmune syndrome involving the exocrine pancreas and other abdominal organs. These experiments establish a novel molecular model of autoimmunity and cast new light on the relationship between thymic selection and immune self-tolerance. Goal of Microarray experiment: We did these experiments to determine how alteration of the function of HDAC7, a site-specific and signal-dependent repressor of transcription, changes gene expression in CD4/CD8 DP thymocytes.
Publication Title
Histone deacetylase 7 regulates cell survival and TCR signaling in CD4/CD8 double-positive thymocytes.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cell-type-specific control of enhancer activity by H3K9 trimethylation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Role of cell-type specific nucleosome positioning in inducible activation of mammalian promoters.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
In fibroblasts, p65-dependent genes can be sub-divided, depending on whether they are Trap-80-dependent or -independent. To examine the generality of this grouping, we performed a microarray analysis of wild-type and Trap-80 knock-down fibroblasts, before and after stimulation of NF-kappaB activity using TNF-alpha.
Publication Title
Two modes of transcriptional activation at native promoters by NF-kappaB p65.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
In dendritic cells, expression of the H3K9me3 demethylase JmjD2d is upregulated by LPS stimulation. To identify genes whose induction by LPS depends on JmjD2d activity, we performed a microarray analysis of wild-type and JmjD2d-knockdown dendritic cells, before and after stimulation with LPS.
Publication Title
Cell-type-specific control of enhancer activity by H3K9 trimethylation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We used microarrays to asses gene expression in 3T3 fibroblasts, after knock-down of Brg1 and Brm using stable shRNA interference. Cells were treated with 5ng/ml mouse TNF-alpha to stimulate inducible gene activation.
Publication Title
Role of cell-type specific nucleosome positioning in inducible activation of mammalian promoters.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Analysis of whole genome gene expression in control and PARKIN patient lines. The hypothesis tested in the present study was that the deficient of PARKIN expression affects multiple pathways. Results provide important information on relationship between PARKIN and mitochondria related gene expression.
Publication Title
Mitochondrial alterations by PARKIN in dopaminergic neurons using PARK2 patient-specific and PARK2 knockout isogenic iPSC lines.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Mus musculus
- 150 Downloadable Samples
- Illumina mouseRef-8 v1.1 expression beadchip
Description
Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending lifespan
Publication Title
Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 47 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip, Illumina humanRef-8 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Age-associated changes in basal NF-κB function in human CD4+ T lymphocytes via dysregulation of PI3 kinase.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Mus musculus
- 72 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Calorie restriction (CR) is the most robust non-genetic intervention to universally delay the onset of age-related diseases and extend mean and maximum lifespan. However, species, strain, sex, diet, age of onset, and level of CR are emerging as important variables to consider for a successful CR response. Here, we investigated the role of strain, sex and level of CR on outcomes of health and survival in mice. Response to CR varied from lifespan extension to no effect on survival, while consistently delaying the onset and impact of diseases independently of strain, sex and level of dietary restriction. CR led to transcriptional and metabolomics changes in the liver indicating anaplerotic filling of the Krebs cycle together with fatty acid fueling of mitochondria. Additionally, CR prevented the age-associated decline in the proteostasis network. Further, CR increased mitochondrial number and preserved their ultrastructure and function with age. Abrogation of mitochondrial function by deletion of fumarate hydratase or malate dehydrogenase 2 negated the life-prolonging effects of CR in yeast and worms. In F1 hybrid strains of mice, the lifespan response to CR tracked with the dam, indicating that the mitochondrial haplotype is an important regulator of CR. Our data illustrate the complexity of the CR responses within a single animal species in the context of aging, with a clear separation of outcomes related to health and survival, highlighting the complexities of translation of CR into human interventions.
Publication Title
Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice.
Sample Metadata Fields
Sex, Specimen part
View Samples