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GSE85858
Mus musculus
12 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Developmentally regulated higher-order chromatin interactions orchestrate B cell fate commitment.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
Description
Organization of the genome in 3D nuclear-space is known to play a crucial role in regulation of gene expression. However, the chromatin architecture that impinges on the B cell-fate choice of multi-potent progenitors remains unclear. By employing in situ Hi-C, we have identified distinct sets of genomic loci that undergo a developmental switch between permissive and repressive compartments during B-cell fate commitment. Intriguingly, we show that topologically associating domains (TADs) represent co-regulated subunits of chromatin and display considerable structural alterations as a result of changes in the cis-regulatory interaction landscape. The extensive rewiring of cis-regulatory interactions is closely associated with differential gene expression programs. Further, we demonstrate the regulatory role of Ebf1 and its downstream factor, Pax5, in chromatin reorganization and transcription regulation. Together, our studies reveal that alterations in promoter and cis-regulatory interactions underlie changes in higher-order chromatin architecture, which in turn determines cell-identity and cell-type specific gene expression patterns.
Publication Title
Developmentally regulated higher-order chromatin interactions orchestrate B cell fate commitment.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
Description
Productive rearrangement of the immunoglobulin heavy chain locus triggers a major developmental checkpoint that promotes limited clonal expansion of pre-B cells, culminating in cell cycle arrest and rearrangement of the kappa () or lambda () light-chain loci. B lineage cells lacking the related transcription factors IRF-4 and IRF-8 undergo a developmental arrest at the cycling pre-B cell stage and are blocked for light-chain recombination. Using Irf-4,8-/- pre-B cells we demonstrate that two pathways converge to synergistically drive light-chain rearrangement, a process that is not simply activated by cell cycle exit. One pathway is directly dependent on IRF-4, whose expression is elevated by pre-BCR signaling. IRF-4 targets the 3 and enhancers to increase locus accessibility and positions a kappa allele away from pericentromeric heterochromatin. The other pathway is triggered by attenuation of IL-7 signaling and results in activation of the intronic enhancer via binding of the transcription factor, E2A. Intriguingly, IRF-4 regulates the expression of CXCR4 and promotes the migration of pre-B cells in response to the chemokine CXCL12. We propose that IRF-4 coordinates the two pathways regulating light-chain recombination by positioning pre-B cells away from IL-7 expressing stromal cells.
Publication Title
Regulation of immunoglobulin light-chain recombination by the transcription factor IRF-4 and the attenuation of interleukin-7 signaling.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 20 Downloadable Samples
Description
These data are from the brains (amygdala and hippocampus) of mice originally derived from a cross between C57BL/6J and DBA/2J inbred strains. We used short-term selection to produce outbred mouse lines with differences in contextual fear conditioning, which is a measure of fear learning. We selected for a total of 4 generations. Fear learning differed in the selected lines and this difference was stronger with each successive generation of selection. These mice also showed differences for measures of anxiety-like behavior, but were not different for tests of non-fear motivated learning, suggesting that selection altered alleles that are specifically involved in emotional behaviors. We identified several QTLs for the selection response. We used Affymetrix microarrays to identify differentially expressed genes in the amygdala and hippocampus of mice from the final generation of selection. Amygdala and hippocampus samples were rapidly dissected out of experimentally nave mice f rom each selected line. Three samples were pooled and hybridized to each array. Experimentally nave mice were used because the behavior of the mice can be reliably anticipated due to their lineage. Thus, these gene expression differences are not due to the response to human handling, foot shock or fear-inducing conditioned stimuli. We have a second similar study that focuses on a different selected population that was based on C57BL/6J and A/J mice (see GES4034).
Publication Title
Selection for contextual fear conditioning affects anxiety-like behaviors and gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Description
The transcription co-factor FOG1 interacts with the chromatin remodeling complex NuRD to mediate gene activation and gene repression during hematopoiesis. We have generated mice with a targeted mutation in the endogenous Fog1 locus that results in an N-ternimal mutation in FOG1 that disrupts the interaction with NuRD.
Publication Title
Pleiotropic platelet defects in mice with disrupted FOG1-NuRD interaction.
Sample Metadata Fields
Specimen part
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