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04.06.15 New publication from Azim Surani’s lab at the Gurdon Institute

last modified Jul 15, 2015 01:51 PM
A paper from Azim Surani's group, in the June 2015 issue of Cell, is the first to describe epigenetic reprogramming in the early human germline.
04.06.15 New publication from Azim Surani’s lab at the Gurdon Institute

Graphical abstract from the paper

A Unique Gene Regulatory Network Resets the Human Germline Epigenome for Development

Tang WWC et al., 2015, Cell volume 161, Issue 6, pp1453–1467

http://dx.doi.org/10.1016/j.cell.2015.04.053 

 

Key findings 

This is the first paper to describe ‘epigenetic reprogramming’ in early human germline, whereby methyl groups attached to specific parts of the DNA are comprehensively erased. DNA demethylation is a bit like using the ‘reset’ button on your electronic device, to wipe the old information and start afresh. The process had been shown in mice but this is the first time it has been shown to occur in human germ cells.

Methylation is one type of epigenetic modification, an influence on gene expression that comes from outside the DNA. At different times during development of a fertilised egg, methyl (CH3) groups attach to Cytosine bases in the DNA, preventing genes from being expressed, and regulating the way that cells differentiate into the many specialised cell types in the body.

But the primordial germ cells, which become eggs and sperm, need an unmodified set of genes so that they form a ‘totipotent’ cell at fertilisation, one that has the complete information to generate every other cell type. Erasure of the methyl groups ensures that the early germ cells can generate a totipotent state. The reprogramming mechanism will also erase almost all ‘epimutations’ from germ cells so that aberrant information is not transmitted to subsequent generations by epigenetic inheritance.

However, the researchers observed that some regions of the genome are resistant to epigenetic reprogramming in the germ cells.  Such ‘escapee’ regions could give rise to transgenerational epigenetic inheritance, i.e. epigenetic changes being transmitted to offspring, affecting how their genes are expressed. These resistant regions included genes that are associated with neural development, neurological disorders such as schizophrenia, and metabolic disorders such as obesity.

DNA methylation also occurs on parts of our DNA that do not code our genes but are called ‘transposable elements’, accumulated through evolution from the DNA of invading organisms. Methylation normally helps keep these elements in check during cell division, preventing them from inserting into our coding DNA and causing mutations.

Demethylation is therefore potentially dangerous for rapidly dividing cells, but the researchers found that some of the transposal elements are also escapees of the reprogramming step, in particular those elements that we have accumulated more recently in evolution.


More about the Surani group


University of Cambridge news item: Reprogramming of DNA observed in human germs cells for first time

Image reproduced from the paper under Creative Commons CC-BY license

Studying development to understand disease

The Gurdon Institute is funded by the Wellcome Trust and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.