This SuperSeries is composed of the SubSeries listed below.
Developmentally regulated higher-order chromatin interactions orchestrate B cell fate commitment.
Specimen part
View SamplesOrganization 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.
Developmentally regulated higher-order chromatin interactions orchestrate B cell fate commitment.
Specimen part
View SamplesProductive 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.
Regulation of immunoglobulin light-chain recombination by the transcription factor IRF-4 and the attenuation of interleukin-7 signaling.
No sample metadata fields
View SamplesWe have determined that sustained expression of EBF suppresses alternate lineage genes independently of Pax5.
Transcription factor EBF restricts alternative lineage options and promotes B cell fate commitment independently of Pax5.
No sample metadata fields
View SamplesLong-lasting activation of T cells requires up-regulation of many genes, for example of transcription factors, cytoskeletal proteins and cell surface proteins encluding ion channels. An increase of ion channel density at the cell surface reflects the needs to manage increased Ca2+ influx into the activated T cell. Using oligonucleotide-based arrays we have surveyed changes in ion channel mRNA expression that occur upon T cell activation. We used Affymetrix Analysis to confirmate our data achieved by self-designed glass array analysis.
A truncation variant of the cation channel P2RX5 is upregulated during T cell activation.
No sample metadata fields
View SamplesIn this study, we used correlation analysis of the expression profiles and carcass traits to produce a list of functional candidate genes under the assumption that genes with strong correlation between their expression values and drip belong to pathways or networks relevant for the control of the trait.
Elucidating molecular networks that either affect or respond to plasma cortisol concentration in target tissues of liver and muscle.
Specimen part
View SamplesThe inverted teat defect is an inherited disorder characterised by the failure of teats to protrude from the udder surface. The number and identity of relevant genes are unknown.
Microarray analysis reveals genes and functional networks relevant to the predisposition to inverted teats in pigs.
Specimen part
View SamplesThe mammary gland development in swine begins at embryogenesis. The number and identity of relevant genes are unknown.
Gene expression analysis of mammary tissue during fetal bud formation and growth in two pig breeds--indications of prenatal initiation of postnatal phenotypic differences.
Specimen part
View SamplesAmyotrophic lateral sclerosis and primary lateral sclerosis are two syndromic variants within the motor neurone disease spectrum. Whilst primary lateral sclerosis is associated with loss of upper motor neurons and a more benign disease course up to 17yrs, amyotrophic lateral sclerosis is caused by loss of both upper and lower motor neurons and has an average disease course of 2-3 years. The majority of cases are sporadic, thereby limiting the availability of cellular models for investigating pathogenic disease mechanisms.
Gene expression signatures in motor neurone disease fibroblasts reveal dysregulation of metabolism, hypoxia-response and RNA processing functions.
Specimen part, Disease
View SamplesIn this study, we used correlation analysis of the expression profiles and carcass traits to produce a list of functional candidate genes under the assumption that genes with strong correlation between their expression values and drip belong to pathways or networks relevant for the control of the trait.
Integrating expression profiling and whole-genome association for dissection of fat traits in a porcine model.
Specimen part
View Samples