Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.800029
Title: The recognition, generation and detection of 5-hydroxymethylcytosine
Author: Bi, Ying
ISNI:       0000 0004 8507 2037
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2020
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Abstract:
5-hydroxymethylcytosine (5hmC) is a DNA modification generated from the oxidation of 5-methylcytosine (5mC) by ten-eleven translocation (TET) enzymes. 5hmC is enriched at promoters, gene bodies and enhancers. The enrichment of 5hmC at the gene body is positively correlated with gene expression. Low levels of 5hmC are observed in various solid tumours and haematological malignancies. The distribution of 5hmC in the genome is strand asymmetric at CG sequences. There are high levels of adjacent and opposing hydroxymethylated and methylated CpG (H/M) sites in the genome. 5hmC in H/M sites account for around 60% of all 5hmC. In this thesis, proteins that specifically recognise H/M sites were identified using DNA pull down followed by LC-MS/MS. However, the binding specificity requires more biochemical validations. The enzymatic pathway that generates H/M site was studied and preliminarily results showed that TET2 have strand selective activity on double strand DNA, which might be a possible way to generate H/M sites. To better understand the distribution of 5hmC in the genome, a 5hmC selective oxidation reaction was applied to map 5hmC on DNA and RNA. The method can be further expended to 5mC mapping in RNA in combination with TET oxidation of 5mC to 5hmC.
Supervisor: Kriaucionis, Skirmantas ; Song, Chunxiao Sponsor: China Scholarship Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.800029  DOI: Not available
Keywords: Genomics ; Epigenetics ; Biochemistry
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