Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Expression of known and predicted genes in tissues of Xenopus tropicalis (frog)

ABSTRACT: Expression of known and predicted genes in tissues of Xenopus tropicalis (frog) pooled from multiple healthy individuals. Two-colour experiments with two different tissues hybridized to each array. Each tissue is arrayed in replicate with dye swaps. Tissues: Brain, Cartilage, Esophagus, Eye, Fat body, Femur, Gallbladder, Heart, Kidney, Large intestine, Liver, Lung, Muscle, Ovary, Oviduct, Skin, Small intestine, Spleen, Stomach, Testis

ORGANISM(S): Xenopus (Silurana) tropicalis

SUBMITTER: Michael Brudno

PROVIDER: E-GEOD-12975 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Conservation of core gene expression in vertebrate tissues.

Chan Esther T ET Quon Gerald T GT Chua Gordon G Babak Tomas T Trochesset Miles M Zirngibl Ralph A RA Aubin Jane J Ratcliffe Michael J H MJ Wilde Andrew A Brudno Michael M Morris Quaid D QD Hughes Timothy R TR

Journal of biology 20090416 3

<h4>Background</h4>Vertebrates share the same general body plan and organs, possess related sets of genes, and rely on similar physiological mechanisms, yet show great diversity in morphology, habitat and behavior. Alteration of gene regulation is thought to be a major mechanism in phenotypic variation and evolution, but relatively little is known about the broad patterns of conservation in gene expression in non-mammalian vertebrates.<h4>Results</h4>We measured expression of all known and predi ...[more]

PMID: 19371447

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Project description:Kabuki Syndrome (KS) is a multisystemic rare disorder, characterized by growth delay, distinctive facial features, intellectual disability, and rarely autism spectrum disorder. This condition is mostly caused by de novo mutations of KMT2D, encoding a catalytic subunit of the COMPASS complex involved in enhancer regulation. KMT2D catalyzes the deposition of histone-3-lysine-4 mono-methyl (H3K4Me1) that marks active and poised enhancers. To assess the impact of KMT2D mutations in the chromatin landscape of KS tissues, we have generated patient-derived induced pluripotent stem cells (iPSC), which we further differentiated into neural crest stem cells (NCSC), mesenchymal stem cells (MSC) and cortical neurons (iN). In addition, we further collected blood samples from 5 additional KS patients. To complete our disease modeling cohort we generated an isogenic KMT2D mutant line from human embryonic stem cells, which we differentiated into neural precursor and mature neurons. Micro-electrode-array (MEA)-based neural network analysis of KS iNs revealed an altered pattern of spontaneous network-bursts in a Kabuki-specific pattern. RNA-seq profiling was performed to relate this aberrant MEA pattern to transcriptional dysregulations, revealing that dysregulated genes were enriched for neuronal functions, such as ion channels, synapse activity, and electrophysiological activity. Here we show that KMT2D haploinsufficiency tends to heavily affect the transcriptome of cortical neurons and differentiated tissues while sparing multipotent states, suggesting that KMT2D has a most prevalent role in terminally differentiated cell and activate transcriptional circuitry unique to each cell type. Moreover, thorough profiling of H3K4Me1 unveiled the almost complete uncoupling between this chromatin mark and the regulatory effects of KMT2D on transcription, which is instead reflected by a defect of H3K27Ac. By integrating RNA-seq with ChIP-seq data we defined TEAD and REST as the master effectors of KMT2D haploinsufficiency. Also, we identified a subset of genes whose regulation is controlled by the balance between KMT2D and EZH2 dosage. Finally, we identified the bona fide direct targets of KMT2D in healthy and KS mature cortical neurons and TEAD2 as the main proxy of KMT2D dysregulation in KS. Overall, our study provides the transcriptional and epigenomic characterization of patient-derived tissues as well as iPSCs and differentiated disease-relevant cell types, as well as the identification of KMT2D direct target in cortical neurons, together with the identification of a neuronal phenotype of the spontaneous electrical activity.

Dataset Information

Expression of known and predicted genes in tissues of Xenopus tropicalis (frog)

Publications

Conservation of core gene expression in vertebrate tissues.

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