New technique offers speed and ease to study imprinted genes at unprecedented coverage

New technique offers speed and ease to study imprinted genes at unprecedented coverage

New technique offers speed and ease to study imprinted genes at unprecedented coverage

Key points:

  • A new fast and cost-effective method for assessing DNA methylation at imprinted genes has been developed by Institute researchers.
  • Correct imprinting is essential for development and failure to do this correctly is associated with development disorders and cancer.
  • The technique overcomes difficulties with studying imprinting and could become the gold standard in both imprinting research and diagnostics, including quality assurance of stem cells in regenerative medicine.

A promising technique offering improvements to both researchers and clinicians has been developed by researchers at the Institute, as described today in the journal Nucleic Acids Research. Application of the technique in a clinical setting could improve the diagnosis of developmental disorders and also ensure the quality of stem cells used in human regenerative medicine.

The IMPLICON technique establishes an easy high-throughput method that can be used to study and check the quality of imprinted genes at multiple sites across the genome. Imprinted genes are genes where only one copy, either the maternally- or paternally-inherited copy, is expressed. They are predominantly regulated by DNA methylation which correlates with expression or silencing. The correct management and expression of imprinted genes is crucial for normal development and dysregulation is associated with developmental defects and cancer. However, despite their importance we lacked a fast and cost-effective method for assessing DNA methylation at imprinted genes.

Lead researcher, Dr Mélanie Eckersley-Maslin, a BBSRC Discovery fellow in the Reik lab, said: “Before the development of this technique, the study of imprinted regions required painstaking region-by-region analysis or expensive whole genome sequencing which needs intensive data analysis. The IMPLICON method provides a targeted approach where only the regions of interest are sequenced but the sequencing provides deep coverage making it robust and more affordable. With the sequencing depth achieved, we believe our method will be better at discerning subtle methylation changes at imprinted regions as a result of environmental perturbations, pathological conditions or ageing, which might never have been sufficiently appreciated using other less powerful imprinting assays.”

Dr Ferdinand von Meyenn, who worked with Dr Eckersley-Maslin on the technique as a research fellow at the Institute, continued: “The technique provides an improved way to check the quality of stem cells and will help to better assess imprinting in many cells as a new quality signature for regenerative medicine.”

The method was conceived and initially developed by researchers in the Reik lab of the Institute’s Epigenetics research programme, who adapted an existing approach and applied it to imprinting for the first time. The team later teamed up with Dr Simão Teixeira da Rocha at the University of Lisbon who helped further developed the assay and applied the human assay to patient stem cell lines.

Dr Simão Teixeira da Rocha, Institute of Molecular Medicine at the University of Lisbon, said: “Being able to quality-check stem cells for correct imprinting before they are used in regenerative medicine is crucial to ensuring patient safety. We need to know that the stem cells retain imprinting fidelity as altered imprinting may cause them to act in undesirable ways. This method provides an easy and comprehensive way to do this for the first time.”

Realising the potential of the technique beyond research, the development of the method was supported by funding from the Institute to support the development of research techniques towards translation. Dr Simon Cook, Head of Knowledge Exchange and Commercialisation, said: “We supported this work through our KEC funding scheme as we could see the potential for imprinting research but also for quality control in the production stem cells for regenerative medicine. It’s great to see this simple assay shared with the wider scientific community!”.

 

Notes to Editors

Publication reference

Klobučar & Kreibich et al. IMPLICON: an ultra-deep sequencing method to uncover DNA methylation at imprinted regions. Nucleic Acids Research

Press contact

Dr Louisa Wood, Communications Manager, Babraham Institute, louisa.wood@babraham.ac.uk

Image description

Digital illustration representing DNA and the concepts of innovation and technology.

Affiliated authors (in author order):

Elisa Kreibich, former Erasmus student in the Reik lab

Felix Krueger, Bioinformatician, Bioinformatics group

Ferdinand von Meyenn, former research fellow in the Reik lab, Epigenetics programme

Mélanie Eckersley-Maslin, BBSRC Discovery fellow, Reik lab

Research funding

This work was supported by a Babraham Institute Translational Advisory Group award to Mélanie Eckersley-Maslin and Ferdinand von Meyenn. Mélanie Eckersley-Maslin is supported by a BBSRC Discovery Fellowship and was supported by an EMBO Fellowship and a Marie Skłodowska-Curie Individual Fellowship.

Additional/related resources:

News, 22 January 2019: Naïve, primed or somewhere in between?

Animal research statement:

As a publicly funded research institute, the Babraham Institute is committed to engagement and transparency in all aspects of its research. The research presented here used DNA samples from mice in order to adapt the technique for use in adult mouse tissues. No animals were specifically bred for this research, the DNA samples used had been collected for other studies. Please follow the link for further details of our animal research and our animal welfare practices.

About the Babraham Institute

The Babraham Institute undertakes world-class life sciences research to generate new knowledge of biological mechanisms underpinning ageing, development and the maintenance of health. Our research focuses on cellular signalling, gene regulation and the impact of epigenetic regulation at different stages of life. By determining how the body reacts to dietary and environmental stimuli and manages microbial and viral interactions, we aim to improve wellbeing and support healthier ageing. The Institute is strategically funded by the Biotechnology and Biological Sciences Research Council (BBSRC), part of UK Research and Innovation, through an Institute Core Capability Grant and also receives funding from other UK research councils, charitable foundations, the EU and medical charities.