RNA Sequencing of sibling and TET2/3 DKO zebrafish
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ABSTRACT:
PROVIDER: PRJNA501894 | ENA |
REPOSITORIES: ENA
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Project description:Ten-eleven translocation (Tet) enzymes (Tet1/2/3) mediate 5-methylcytosine (5mC) hydroxylation, which can facilitate DNA demethylation and thereby impact gene expression. Studied mostly for how mutant isoforms impact cancer, the normal roles for Tet enzymes during organogenesis are largely unknown. By analyzing compound mutant zebrafish, we discovered a requirement for Tet2/3 activity in embryonic heart for recruitment of epicardial progenitors, associated with defects in development of the atrial-ventricular canal (AVC). Through a combination of methylation, hydroxymethylation, and transcript profiling, the genes encoding the ActivinA subunit Inhbaa (in endocardium) and Sox9b (in myocardium) were implicated as demethylation targets of Tet2/3 and critical for organization of AVC-localized extracellular matrix (ECM), facilitating migration of epicardial progenitors onto the developing heart tube. This study elucidates essential DNA epigenetic modifications that govern gene expression changes during cardiac development with striking temporal and lineage specificities, highlighting complex interactions in multiple cell populations during development of the vertebrate heart.
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Project description:Transcriptional profiling of hdac1 mutant zebrafish in comparison to their sibling embryos. Embryos resulting from a cross between heterozygous hdac1 mutant zebrafish (hi1618/+) where cultured together then mutants separated from the siblings one the basis of phenotype and RNA extracted from the two groups at 27hpf was compared in a two-colour hybridisation. Two-condition experiment, hdac1 mutants vs. sibling. Biological replicates: 2 (separate mating) Technical replicates: 4 (2 of which are dye-swap)
2011-01-21 | E-GEOD-26707 | biostudies-arrayexpress
Project description:Transcriptional profiling of hdac1 mutant zebrafish in comparison to their sibling embryos. Embryos resulting from a cross between heterozygous hdac1 mutant zebrafish (hi1618/+) where cultured together then mutants separated from the siblings one the basis of phenotype and RNA extracted from the two groups at 27hpf was compared in a two-colour hybridisation.
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Project description:Zebrafish hematopoietic cells from kidney marrow from zebrafish tet2 mutants were compared to wild-type
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Project description:Zebrafish hematopoietic cells from kidney marrow from zebrafish tet2 mutants were compared to wild-type
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Project description:Zebrafish primary neurons either sfpq sibling/control (+/+, +/-) or null (-/-) were cultured in transwell inserts. At DIV2, for each genotype, cellular and neurite tissues were separately isolated, RNA extracted and total RNAseq performed.
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Project description:To identify the underlying mechanism causing the defects in light-dependent behavioral rhythm formation and the reduced locomotor activity in DKO and TKO zebrafish, a microarray analysis was conducted.
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Project description:Functional genomic analysis of WT, Tet1-/-, Tet2-/-, Tet1-/-:Tet2-/- (DKO) murine embryonic stem cells
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Project description:TET1/2/3 are methylcytosine dioxygenases regulating cytosine hydroxymethylation in the genome. Tet1 and Tet2 are abundantly expressed in HSC/HPCs and implicated in the pathogenesis of hematological malignancies. Tet2-deletion in mice causes myeloid malignancies, while Tet1-null mice develop B-cell lymphoma after an extended period of latency. Interestingly, TET1 and TET2 were often concomitantly down-regulated in acute B-lymphocytic leukemia. Here, we investigated the overlapping and non-redundant functions of Tet1/Tet2 in HSC maintenance and development of hematological malignancies using Tet1/2 double knockout (DKO) mice. DKO and Tet2-/- HSC/HPCs had overlapping and unique 5hmC and 5mC profiles and behaved differently. DKO mice exhibited strikingly decreased incidence and delayed onset of myeloid malignancies compared to Tet2-/- mice and in contrast developed lethal B-cell malignancies. Transcriptome analysis of DKO tumors revealed expression changes in many genes dysregulated in human B-cell malignancies, such as LMO2, BCL6 and MYC. These results highlight the critical roles of TET1 or TET2 individually and their cross-talks in the pathogenesis of hematological malignancies. Given the role of Tet proteins in 5mC oxidation, we employed a previously established chemical labeling and affinity purification method coupled with high-throughput sequencing (hMe-Seal) to profile the genome-wide distribution of 5hmC, as well as methylated DNA immunoprecipitation (MeDIP) coupled with high-throughput sequencing (MeDIP-seq) to profile 5mC using BM LK cells purified from young WT, Tet2-/- and DKO mice (6-10 wks old).
2015-11-12 | E-GEOD-73611 | biostudies-arrayexpress
Project description:Tet enzymes (Tet1/2/3) convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Tet1 and Tet2 mediate 5hmC generation in mouse embryonic stem cells (ESCs) and various embryonic and adult tissues. To investigate the effects of combined deficiency of Tet1 and Tet2 on pluripotency and development, we have generated Tet1 and Tet2 double knockout (DKO) ESCs and mice. DKO ESCs were depleted of 5hmC, but remained pluripotent with subtle defects in differentiation and changes in gene expression. Double mutant embryos and chimeras exhibited mid-gestation defects and postnatal DKO mice displayed partially penetrant neonatal lethality and stochastic perturbation of imprinting. Viable DKO animals developed normally to adulthood but had reduced 5hmC level, increased 5mC level and lacked 5hmC in germ cells. Nevertheless, DKO mice of both sexes were fertile with females having smaller ovaries and reduced fertility. Our data suggest that both Tet1 and Tet2 contribute to 5hmC levels during development. Their combined loss does not block differentiation and embryogenesis, but leads to partially penetrant embryonic and perinatal abnormalities and compromised viability. Moreover, the presence of substantial levels of 5hmC in DKO embryos and adult mice suggests a significant contribution of Tet3 in hydroxylation of 5mC during development. Methylation patterns in tissue samples from a series of wt and Tet1/Tet2 DKO embryos, neonates and adults were generated using methylated DNA immunoprecipitation with antibodies against 5mC (MeDIP) and 5hmC (hMeDIP) followed by deep sequencing.
2013-02-01 | E-GEOD-42396 | biostudies-arrayexpress