Role of cytidine deaminases in epigenetic reprogramming and demethylation of DNA

Lead Research Organisation: Babraham Institute
Department Name: UNLISTED

Abstract

Genetic information is passed from generation to generation and is the material upon which natural selection acts. On top of this genetic information the genome also contains epigenetic information in the form of chemical and other modifications to DNA, which are associated with gene expression and genome function. Epigenetic mechanisms of gene regulation are of key importance in development, stem cell biology and regenerative medicine, and cancer. During certain periods of early development of an embryo, epigenetic modifications including DNA methylation are reprogrammed on a genome wide level. This may be important in order to establish totipotency (the ability to give rise to an entire organism) of the embryonic genome. The mechanisms of the removal of DNA methylation from the genome are unknown in mammals. This student project investigates a class of candidate enzymes in the mouse which have been shown to be able to chemically alter methylated cytosines. There are four of these candidate genes in the mouse genome, for three of which we have knockout mutations (to create 'inactive' genes). A fourth knockout is being constructed, and knockouts will then be examined for altered DNA methylation and development. If methylated cytosines are chemically altered, the DNA needs to be repaired following this event. The project also investigates the DNA repair pathways which would be responsible.

Publications

10 25 50
 
Description EU NoE EpiGeneSys
Amount £400,000 (GBP)
Funding ID 257082 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start  
 
Description MRC Collaboration Grant (deep sequencing in Epigenomics)
Amount £960,000 (GBP)
Funding ID G0801156 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start  
 
Title Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation 
Description Sequence submitted to online database (ENA/SRA) 
Type Of Material Database/Collection of data 
Year Produced 2011 
Provided To Others? No  
Impact No actual impacts realised to date 
URL http://www.ebi.ac.uk/ena/data/view/ERP000570&display=html
 
Description MRC EASIH 
Organisation University of Cambridge
Department Cambridge Institute for Medical Research (CIMR)
Country United Kingdom 
Sector Academic/University 
PI Contribution increased opportunities for deep sequencing using alternative platforms such as Roche 454 and ABI Solid
Collaborator Contribution MRC East Anglia Sequencing and Informatics Hub established in 2009
Impact see above
Start Year 2009
 
Title IP assignment 
Description CellCentric IP waiver agreement 
IP Reference  
Protection Protection not required
Year Protection Granted 2014
Licensed Commercial In Confidence
Impact None expected