| EPSRC Reference: |
EP/J007587/1 |
| Title: |
Chemical Strategies for Epigenome Wide Discrimination of 5-Hydroxymethylcytosine and 5-Methylcytosine |
| Principal Investigator: |
Bradley, Professor M |
| Other Investigators: |
|
| Researcher Co-Investigators: |
|
| Project Partners: |
|
| Department: |
Sch of Chemistry |
| Organisation: |
University of Edinburgh |
| Scheme: |
Standard Research |
| Starts: |
01 November 2012 |
Ends: |
31 October 2015 |
Value (£): |
529,710
|
| EPSRC Research Topic Classifications: |
| Biological & Medicinal Chem. |
|
|
| EPSRC Industrial Sector Classifications: |
| No relevance to Underpinning Sectors |
|
|
| Related Grants: |
|
| Panel History: |
| Panel Date | Panel Name | Outcome |
|
08 Sep 2011
|
EPSRC Physical Sciences Chemistry - September 2011
|
Announced
|
|
|
Summary on Grant Application Form |
Methylation of cytosine is a major modification of the mammalian genome generally associated with gene repression and regulation, with alteration of 5-methylcytosine patterns during development contributing to the regulation of gene expression and cell specification. Given its importance methods of so-called bisulfite sequencing have been developed that allow comparative 5-methylcytosine/cytosine analysis of Genomic DNA.
However in addition to 5-methyl-C another cytosine modification, 5-hydroxymethylcytosine (5-hydroxymethyl-C or 5-hmC) has recently been identified as an epigenetic modification. In humans, mutations in the enzymes that make hydroxymethyl-C are associated with myeloid malignancies. Evidence also suggests that's that 5-hydroxymethyl-C is an epigenetic marker of "stem-cellness" and neuronal lineage specification.
However current DNA sequencing techniques cannot differentiate between 5-methyl-C and 5-hydroxymethyl-C. Indeed it is certain that previous studies have misread 5-hydroxymethyl-C as 5-methyl-C. The presence of 5-hydroxymethyl-C makes it necessary to not only re-evaluate existing DNA methylation data, but also to develop a new method to determine the relative distribution and changes of 5-hydroxymethyl-C in human tissues of healthy and diseased status. The basis of this proposal is to develop chemistry based approaches to allow the genome wide analysis of 5-methyl-C and 5-hydroxymethyl-C.
|
|
Key Findings |
|
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
|
|
Potential use in non-academic contexts |
|
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
|
|
Impacts |
|
| Description |
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk |
| Summary |
|
| Date Materialised |
|
|
|
|
Sectors submitted by the Researcher |
|
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
|
| Project URL: |
|
| Further Information: |
|
| Organisation Website: |
http://www.ed.ac.uk |