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A glitch in the analysis of genomic DNA methylation:
July 2010
In a collaborative effort between the Human Genetics Unit (MRC Human Genetics Unit, Institute of Genetics Molecular Medicine) and the Breakthrough Breast Cancer Research Unit, Dr Donncha Dunican, Dr Richard Meehan and colleagues (Nestor et al. Biotechniques 48(4):317–319, 2010) have discovered a gremlin in the analysis of genomic DNA methylation. Their work was inspired by the identification of the novel mammalian DNA modification, 5-hydroxymethylcytosine in 2009.
A mark of this nature is anticipated to play roles in transcription regulation, DNA repair and potentially cancer. Using in vitro approaches, the group demonstrated that the intensely studied DNA methylation and novel DNA hyrodxymethylation marks are indistinguishable using state-of-the-art DNA methylation technologies.
Dr Dunican said:
"Our original aim was to carry out pilot experiments with hydroxymethylated DNA. Once we got started, we quickly realised that the epigenetics community (and other fields) would be keen to learn that existing classical DNA methylation datasets are likely to include latent hydroxymethylated bases."
As of yet the precise function of hydroxymethylation on DNA is unknown, however Dr Dunican added: "As antibodies to hydroxymethylated DNA have become commercially available, we are now in a strong position to ask where this mark resides in the genome (and cancer genomes) to gain much needed functional insights".
Links
- Breakthrough Breast Cancer
- Dr Richard Meehan (Medical Research Council Human Genetics Unit)
- PubMed link: Enzymatic approaches and bisulfite sequencing cannot distinguish between 5-methylcytosine and 5-hydroxymethylcytosine in DNA.
Prestigious MRC Career Development Award:
August 2010
Dr Gracjan Michlewski has been awarded a prestigious MRC Career Development Award to establish his independent laboratory at the Wellcome Trust Centre for Cell Biology in Edinburgh. This £1,500,000 award will fund a five-year project focused on "Regulation of microRNA Biogenesis and Function in Humans".
Recently, it has been recognized that RNAs are not only mere messengers but also serve as active elements that control various processes in human cells. It has been discovered that a group of small RNAs, called microRNAs, play a central role in the control of protein production. They are required for normal development and functioning of the human body. Moreover, microRNA levels are frequently changed in many human disorders, such as cancer, which suggest their contribution towards pathology and provide potential targets for new therapies.
The goal of this project is to understand the contribution of microRNAs in the control of protein production. In particular, the study is aimed to reveal how specific microRNAs are generated and what are the mechanisms that control their levels in human cells.
Links
- Michlewski, G.; Guil, S.; Semple, C.A. & Cáceres, J.F. Posttranscriptional regulation of miRNAs harboring conserved terminal loops. Mol. Cell 32:383–393, 2008 PubMed
- Michlewski, G. & Cáceres, J.F. Antagonistic role of hnRNP A1 and KSRP in the regulation of let-7a biogenesis. Nature Structural & Molecular Biology 17:1011–1018, 2010 PubMed
