Characterization of hundreds of regulatory landscapes in developing limbs reveals two regimes of chromatin folding Overall design: RNA-seq
Characterization of hundreds of regulatory landscapes in developing limbs reveals two regimes of chromatin folding.
Specimen part, Cell line, Subject
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The BTB and CNC homology 1 (BACH1) target genes are involved in the oxidative stress response and in control of the cell cycle.
Cell line, Time
View SamplesBTB and CNC homology 1 (BACH1) is a heme-binding transcription factor repressing the transcription from a subset of MAF recognition elements (MAREs) at low intracellular heme levels. Upon heme binding, BACH1 is released from the MAREs, resulting in increased expression of antioxidant response genes. To systematically address the gene regulatory networks involving BACH1, we performed knock-down of BACH1 in HEK 293T cells using three independent types of small interfering RNAs followed by transcriptome profiling using microarrays.
The BTB and CNC homology 1 (BACH1) target genes are involved in the oxidative stress response and in control of the cell cycle.
Cell line, Time
View SamplesTranscriptome of HEK and B cells were analyzed by microarray and RNA-Seq parallely. Both platforms were then compared in terms of sensitivity. To assess whether values were a reliable indicator of gene activity, we correlated these values with hypophosphorylated RNA polymerase II (PolIIa) occupancy, used as a landmark of transcription initiation. For HEK, we identified PolIIa islands by chromatin immunoprecipitation and sequencing (ChIP-Seq).
A global view of gene activity and alternative splicing by deep sequencing of the human transcriptome.
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View SamplesDuring embryogenesis, enhancer-promoter interactions control gene transcriptional activation. These interactions can be tissue-specific or tissue-invariant and occur mostly within larger insulated regulatory domains called Topologically Associating Domains (TADs). Boundary elements, which delineate the extent of TADs, frequently interact with each other and have been associated with constitutive transcription and CTCF/Cohesin binding. In this work, we set out to investigate the regulatory role of a tissue-invariant, preformed interaction between two boundaries that involve the Shh gene and its unique limb enhancer, the ZRS, located one megabase away. Using CRISPR/Cas9 we specifically perturb CTCF binding sites or constitutive transcription at the ZRS-containing boundary, without altering the enhancer sequence. Using capture-HiC (cHiC) we show that both types of perturbation result in altered preformed chromatin interactions and lead to a reduction of Shh expression in developing limb buds. Finally, we demonstrate that the disruption of the chromatin structure in combination with a hypomorphic ZRS allele results in a dramatic Shh loss- of- function and digit agenesis. We thus propose that preformed chromatin structures can ensure stable enhancer promoter communication during development and robustness of gene transcriptional activation. Overall design: We performed transcriptome analysis to confirm the complete loss of the Lmbr1 transcript due to the deletion of its promoter and to detect other potential non-coding transcripts at the locus.
Preformed chromatin topology assists transcriptional robustness of <i>Shh</i> during limb development.
Cell line, Subject
View SamplesCNS autoimmunity is induced by autoreactive T cells reactive against CNS antigen. However how these T cells become able to transgress the blood brain barrier is not CNS autoimmunity is induced by autoreactive T cells reactive against CNS antigen. Here a gene expression profile of the pathogenic T cells in different functional states was performed.
T cells become licensed in the lung to enter the central nervous system.
Sex, Specimen part
View SamplesGenome-scale methods have identified subchromosomal structures so-called topologically associated domains (TADs) that subdivide the genome into discrete regulatory units, establish with their target genes. By re-engineering human duplications at the SOX9 locus in mice combined with 4C-seq and Capture Hi-C experiments, we show that genomic duplications can result in the formation of novel chromatin domains (neo-TADs) and that this process determines their molecular pathology. Overall design: RNA-seq of embryonic limb buds for WT and mutant animals carrying structural variations at the Sox9/Kcnj locus.
Formation of new chromatin domains determines pathogenicity of genomic duplications.
Specimen part, Subject
View SamplesChemokines have been suggested to play a role during development of left ventricular failure, but little is known about their role during right ventricular (RV) remodeling and dysfunction. The first aim of this study was to identify chemokines which are regulated during RV pressure overload. We then hypothesized that these chemokines regulate SLRPs (small leucine-rich proteoglycans)
Chemokines regulate small leucine-rich proteoglycans in the extracellular matrix of the pressure-overloaded right ventricle.
Sex, Specimen part, Disease
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Combinatorial recruitment of CREB, C/EBPβ and c-Jun determines activation of promoters upon keratinocyte differentiation.
Specimen part, Treatment
View SamplesCombinatorial recruitment of CREB, C/EBPb and Jun determines activation of promoters upon keratinocyte differentiation
Combinatorial recruitment of CREB, C/EBPβ and c-Jun determines activation of promoters upon keratinocyte differentiation.
Specimen part, Treatment
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