In mice and other mammals the suprachiasmatic nuclei (SCN) within the brain, synchronises daily rhythms in metabolism, physiology and behaviour to the Earth's local time. Whilst much is known about the SCN's time keeping mechanism, less is known about how it adjusts or resets timing to changes in local time beyond the induction of CRE regulated genes and the differential response of dorsal and ventral sub-regions of the SCN after light exposure known to advance rhythms.
No associated publication
Specimen part, Treatment
View SamplesThyroid hormone is crucial for normal brain development. Thyroid hormone transporters control thyroid hormone homeostatis in brain. Mutations in the thyroid hormone transporter MCT8 result in a complex endocrine and neurological phenotype.
Transcriptional profiling of fibroblasts from patients with mutations in MCT8 and comparative analysis with the human brain transcriptome.
Specimen part
View SamplesDuring B cell development the precursor B cell receptor (pre-BCR) checkpoint is thought to increase immunoglobulin k light chain (Igk) locus accessibility to the V(D)J recombinase. Accordingly, pre-B cells lacking the pre-BCR signaling molecules Btk or Slp65 showed reduced germline Vk transcription. To investigate whether pre-BCR signaling modulates Vk accessibility through enhancer-mediated Igk locus topology, we performed chromosome conformation capture and sequencing analyses. These revealed that already in pro-B cells the k enhancers robustly interact with the ~3.2 Mb Vk region and its flanking sequences. Analyses in wild-type, Btk and Slp65 single and double-deficient pre-B cells demonstrated that pre-BCR signaling reduces interactions of both enhancers with Igk locus flanking sequences and increases interactions of the 3k enhancer with Vk genes. Remarkably, pre-BCR signaling does not significantly affect interactions between the intronic enhancer and Vk genes, which are already robust in pro-B cells. Both enhancers interact most frequently with highly used Vk genes, which are often marked by transcription factor E2a. We conclude that the k enhancers interact with the Vk region already in pro-B cells and that pre-BCR signaling induces accessibility through a functional redistribution of long-range chromatin interactions within the Vk region, whereby the two enhancers play distinct roles.
Pre-B cell receptor signaling induces immunoglobulin κ locus accessibility by functional redistribution of enhancer-mediated chromatin interactions.
Specimen part
View SamplesNIH3T3 cells were irradiated with 8Jm-2 UVC using a Philips TUV germicidal lamp and 4 hours later total RNA was isolated.
No associated publication
Cell line
View SamplesWe have analysed a family with an autosomal recessive type of tetraplegic cerebral palsy with mental retardation, reduction of cerebral white matter, and atrophy of the cerebellum in an inbred sibship.
Mutation in the AP4M1 gene provides a model for neuroaxonal injury in cerebral palsy.
Sex, Specimen part
View SamplesRecent studies have suggested that deregulated AKT1 signaling is associated with schizophrenia. We hypothesized that if this is indeed the case, we should observe both decreased AKT1 expression as well as deregulation of AKT1 regulated pathways in Peripheral Blood Mononuclear Cells (PBMCs) of schizophrenia patients. We therefore examined PBMC expression levels of AKT1 in schizophrenia patients versus controls, and examined whether functional biological processes in which AKT1 plays an important role are deregulated in schizophrenia patients. We performed a case-control study, investigating whole-genome PBMC gene expression in male, recent onset (<5 years) schizophrenia patients (N=43) as compared to controls (N=29). Genes, differentially expressed between patients and controls were identified using ANOVA with Benjamini-Hochberg correction (false discovery rate (FDR)= 0.05). Functional aspects of the deregulated set of genes were investigated with the Ingenuity Pathway Analysis (IPA) Software Tool.
No associated publication
Sex, Specimen part, Disease, Disease stage
View SamplesMicroarrays were used to detail the global programme of gene expression underlying breast cancer cell lines. We identified two main groups of luminal-type and basal-type breast cancer cell lines by unsupervised Pearson correlation of breast cancer cell lines and intrinsic subtyping. Supervised analysis on spindle versus non-spindle breast cancer cell lines identified a spindle cell signature of 1,144 genes identifying all spindle, basal-type, E-cadherin methylated breast cancer cell lines.
No associated publication
Specimen part, Cell line
View SamplesTitle: Transcriptome analysis of human endometrial tissues from healthy post-menoupausal women reflecting the endometrial response to 3-weeks treatment with tibolone, E2 and E2+MPA.
Molecular analysis of human endometrium: short-term tibolone signaling differs significantly from estrogen and estrogen + progestagen signaling.
No sample metadata fields
View SamplesTranscription regulation involves enzyme-mediated changes in chromatin structure. Here, we describe a novel mode of histone crosstalk during gene silencing, in which histone H2A monoubiquitylation is coupled to the removal of histone H3 Lys 36 dimethylation (H3K36me2). This pathway was uncovered through the identification of dRING-associated factors (dRAF), a novel Polycomb group (PcG) silencing complex harboring the histone H2A ubiquitin ligase dRING, PSC and the F-box protein, and demethylase dKDM2. In vivo, dKDM2 shares many transcriptional targets with Polycomb and counteracts the histone methyltransferases TRX and ASH1. Importantly, cellular depletion and in vitro reconstitution assays revealed that dKDM2 not only mediates H3K36me2 demethylation but is also required for efficient H2A ubiquitylation by dRING/PSC. Thus, dRAF removes an active mark from histone H3 and adds a repressive one to H2A. These findings reveal coordinate trans-histone regulation by a PcG complex to mediate gene repression.
dKDM2 couples histone H2A ubiquitylation to histone H3 demethylation during Polycomb group silencing.
Cell line
View SamplesAcute Myeloid Leukemia (AML) is a heterogeneous disease from the molecular and biological standpoints, and even patients with a specific gene expression profile may present clinical and molecular heterogeneity. We studied the epigenetic profiles of a cohort of patients that shared a common gene expression profile but differed in that only half of them harbored mutations of the CEBPA locus, while the rest presented with silencing of this gene and co-expression of certain T cell markers. DNA methylation studies revealed that these two groups of patients could be readily segregated in an unsupervised fashion based on their DNA methylation profiles alone. Furthermore, CEBPA silencing was associated with the presence of an aberrant DNA hypermethylation signature, which was not present in the CEBPA mutant group. This aberrant hypermethylation occurred more frequently at sites within CpG islands. CEBPA silenced leukemias also displayed marked hypermethylation when compared with normal CD34+ hematopoietic cells, while CEBPA mutant cases showed only mild changes in DNA methylation when compared to these normal progenitors. Biologically, CEBPA silenced leukemias presented with a decreased response to myeloid growth factors in vitro.
Genome-wide epigenetic analysis delineates a biologically distinct immature acute leukemia with myeloid/T-lymphoid features.
No sample metadata fields
View Samples