April 3, 2011

experts reactions to new research on epigenetics and stem cell reprogramming as published in Nature

Environmental impacts on gene regulation may have an impact on stem cell development, according to new research.

Prof Robin Lovell-Badge, Head of Division, National Institute for Medical Research (NIMR), said:

“This is a very nice study with some important findings. Methylation of DNA has been studied for a long time and it is important for gene activity or inactivity. In this paper a far less-well studied DNA modification, hydroxymethylation, has been looked at, which seems to have opposite effects.

“Moreover their evidence suggests that it is functionally important. It will be something else to explore during embryonic development and particularly when reprogramming cells, for example when deriving iPS cells, to make sure that these types of DNA modification have occurred in all the appropriate places. However, the authors have not yet looked at this.”

Prof Marcus Pembrey, Emeritus Professor of Paediatric Genetics, Institute of Child Health, UCL, said:

“Enduring changes in gene activity during embryological development and beyond are maintained by methyl chemical groups being added to the DNA of control regions of certain genes.

“How DNA methylation – the mainstay of our cellular memory system – happens has been known for decades but not how methyl groups are removed, for example between generations. This paper (and studies of human brain by Gerd Pfeifer)* show that chemical modification of the methyl groups themselves (hydroxy methyl) is occurring at critical places in the genome after fertilisation and in embryonic stem cells. Is this a key part of epigenetic regulation or a bystander effect? It needs further work but represents a valuable new insight.”

Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation, Gabriella Ficz, Miguel R. Branco, Wolf Reik, published in Nature at 18:00, Sunday 3 April. * Genomic mapping of 5-hydroxymethylcytosine in the human brain, Seung-Gi Jin, Xiwei Wu, Arthur X. Li and Gerd Pfeifer, Nucl. Acids Res. , 2011, first published online March 4, 2011 doi:10.1093/nar/gkr120