Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 23 for “"TET2"”.
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Characterization of 5-methylcytosine dioxygenase Tet2 and rescue of mutant Tet2 activity by using turbo co-substrate
… base excision repair. Inactivation of the TET2 gene due to genetic mutations or other epigenetic mechanisms is associated with poor prognosis in patients with diverse cancers, especially hematopoietic malignancies. Herein, we describe an efficient single-step purification of enzymatically …
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The Effects of TET2-Deficiency on Neutrophil Gene Expression and Function
… methylcytosine dioxygenase 2 (TET2) variants are common in CHIP and associate with epigenetic dysregulation, inflammation, and cardiovascular disease. Although neutrophils are sensitive to epigenetic dysregulation and contribute to many cardiovascular diseases, the effects of …
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Characterising the role of TET2 in oestrogen receptor positive breast cancer
… the participation of the dioxygenase enzyme TET2 in the ER complex. The remainder of the thesis investigates the contribution of TET2 to ER biology. Quantitative multiplexed rapid immunoprecipitation mass spectrometry of endogenous proteins (qPLEX-RIME) was used to assess changes to the ER …
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The role of Ten Eleven Translocation enzymes in the hair follicle mesenchyme
… can provide complete reversal of hair loss. Tet2 promotes DNA demethylation by the hydroxylation of 5mC to 5hmC which in turn causes gene transcription activation. Dermal papilla (DP) cells located within the hair follicle are responsible for the regulation of development and the growth of …
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Single-cell approaches reveal functional and molecular heterogeneity in malignant haematopoietic stem cells
… by crossing JAK2 V617F mice with mice lacking TET2, the most commonly co-mutated gene in patients with MPN. Single-cell gene expression profiling of JAK2 V617F-mutant HSCs revealed reduced expression of specific self-renewal regulator genes, some of which were restored to normal levels in …
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Metabolomics and chemical library screening for antibacterial drug discovery
… the activity of Ten-Eleven Translocation 2 (TET2) enzyme. Methylation of one of the DNA bases, cytosine at the C-5 position (5-methylcytosine, 5mC) plays a crucial role in epigenetic transcriptional regulation. TET-family dioxygenases (TET1, TET2 and TET3) initiate active demethylation of …
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The Role of Dna Methylation and Hydroxymethylation In Smooth Muscle Cell Phenotypic Change During Atherogenesis
… gene. Results detail the identification of TET2 as an epigenetic regulator that acts upstream of IGF-1R during atherogenesis through demethylation of the promoter area. We further show that TET2 mRNA and protein were found to be regulated by the mTORC1 signaling pathway, and selective …
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Investigating clonal hematopoiesis in rhesus macaque and human
… mutated in human CH, with *DNMT3A* and *TET2* mutations being the most frequent. Of the 60 aged RM (median age of 25 years), 12 (20%) were to carry naturally occurring driver CH mutations and showed a trend of increasing with age. On the other hand, in the autologous transplantation RM …
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Clonal haematopoiesis of indeterminate potential and the role of inflammation in its association with atherosclerosis
… activity and IL-1β release are increased by Tet2 loss, and reduced by Dnmt3a mutation, despite both perturbations upregulating transcript for IL-1β. Conversely, Jak2 mutations have no effect on macrophage cytokine production or release. Therefore, immunomodulatory therapies under …
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Behavioural, genetic and epigenetic determinants of white matter pathology in a new mouse model of chronic cerebral hypoperfusion
… and/ or Ten- eleven translocation proteins (e.g. TET2) in mice. DNA methylation (5mC), hydroxymethylation (5hmC) and TET2 were immunochemically studied in white and grey matter of sham and chronically hypoperfused C57Bl6J mice a month after surgery. The immunochemical results demonstrated …
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Molecular Insights of Primary Thyroid B-cell Lymphomas by Somatic Genetic and Immunogenetic Profiling
… and often concurrent deleterious mutations in *TET2* (86%), *TNFRSF14* (53%) and *CD274* (53%), which are absent or rarely seen in EMZL of other anatomic sites. Such distinct mutation profiles may be due to the influence of aetiology on the acquisition and selection of genetic changes that …
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ELUCIDATION OF MECHANISMS GENERATING 5-HYDROXYMETHYLCYTOSINE (5hmC) IN MAMMALIAN MITOCHONDRIA
… Tet family of methylcytosine dioxygenases(Tet1, Tet2 and Tet3) was found to catalyze the oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), an intermediate in the pathway of DNA demethylation. Tet enzymes catalyze this hydroxylation in a 2-oxoglutarate and Fe2+ dependent …
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Epigenetic Regulation Of The HIF Pathway And Novel Therapeutic Opportunities
… inhibit the amplification of the HIF pathway. TET2 is a Fe(II), 2OG dependent dioxygenase which can demethylate 5mC in a CpG context, a key epigenetic modification. In this study we developed a HPLC based analytical method for evaluating the catalysis by recombinant TET2 protein
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Developmental Dynamics of 5-Hydroxymethylcytosine and its Role in the Terminal Differentiation of Neurons
… division. Deletion of the 5hmC writers Tet1, Tet2, and Tet3 from postmitotic Purkinje cells alters cytosine modification in regulatory domains, impairs gene expression, hinders developmental transitions, and causes hyper-excitability and increased susceptibility to excitotoxic drugs. These …
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Understanding the role of extrinsic regulators in normal and malignant haematopoiesis
… disease subtype and associated with JAK2 and TET2 mutational status in both patients and mouse models (Chapter 5). Together, these findings highlight the importance of the extrinsic regulators and the haematopoietic microenvironment in influencing cellular outcomes in both the normal and …
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Modelling timing in blood cancers
… Neoplasms patients with both JAK2 and TET2 mutations have different disease characteristics with distinct mutation order. My analyses identify HOXA9 as a potential prognosis marker and biological switch responsible for patient stratification in these patients and in Acute Myeloid …
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The natural history of clonal haematopoiesis
… only drove expansion later in life, while TET2-mutant clones emerged across all ages. Using a separate cohort of 158 twins, we found that concordance for CH was no higher within monozygotic vs dizygotic pairs, suggesting that the inherited genome does not exert a dominant influence on CH …
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Investigating the clinicopathological spectrum and associated genetics of colorectal carcinoma in young (<60 years of age) patients in the Western Cape Province
… pathway alterations were similar. FAT4 (26%) and TET2 (15%) have emerged as important novel driver genes in left-sided tumours, and potential therapeutic targets for further investigation.
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Identification of Novel Drivers of Haematopoietic Stem Cell Fate Using Low Cell Number Proteomics and Single Cell Profiling
… with increasing self-renewal potency, including TET2-deficient HSCs exhibiting a self-renewal advantage in MPN mouse models. Here, we observed reshaping of extracellular matrix protein networks, indicating a potential physical role of the neighbouring bone marrow niche cells for regulating HSC …
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