Life Sciences Research for Lifelong Health

Wolf Reik

Research Summary

Epigenetic modifications such as DNA methylation and histone marks are often relatively stable in differentiated and in adult tissues in the body, where they help to confer a stable cell identity on tissues. The process of epigenetic reprogramming, by which many of these marks are removed from DNA, is important for the function of embryonic stem cells and in reprogramming stem cells from adult tissue cells. When this erasure goes wrong there may be adverse consequences for healthy development and ageing, which can potentially extend over more than one generation.

​Our insights into the mechanisms of epigenetic reprogramming may help with developing better strategies for stem cell therapies and to combat age related decline. We have also recently initiated work on epigenetic regulation of social behaviours in insects, where we are interested in how patterning and regulation of DNA methylation in the brain is linked with the evolution of sociality.

Latest Publications

DNA methylation homeostasis in human and mouse development.
Iurlaro M, von Meyenn F, Reik W

The molecular pathways that regulate gain and loss of DNA methylation during mammalian development need to be tightly balanced to maintain a physiological equilibrium. Here we explore the relative contributions of the different pathways and enzymatic activities involved in methylation homeostasis in the context of genome-wide and locus-specific epigenetic reprogramming in mammals. An adaptable epigenetic machinery allows global epigenetic reprogramming to concur with local maintenance of critical epigenetic memory in the genome, and appears to regulate the tempo of global reprogramming in different cell lineages and species.

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Current opinion in genetics & development, 43, 1879-0380, 101-109, 2017

PMID: 28260631

The Ageing Brain: Effects on DNA Repair and DNA Methylation in Mice.
Langie SA, Cameron KM, Ficz G, Oxley D, Tomaszewski B, Gorniak JP, Maas LM, Godschalk RW, van Schooten FJ, Reik W, von Zglinicki T, Mathers JC

Base excision repair (BER) may become less effective with ageing resulting in accumulation of DNA lesions, genome instability and altered gene expression that contribute to age-related degenerative diseases. The brain is particularly vulnerable to the accumulation of DNA lesions; hence, proper functioning of DNA repair mechanisms is important for neuronal survival. Although the mechanism of age-related decline in DNA repair capacity is unknown, growing evidence suggests that epigenetic events (e.g., DNA methylation) contribute to the ageing process and may be functionally important through the regulation of the expression of DNA repair genes. We hypothesize that epigenetic mechanisms are involved in mediating the age-related decline in BER in the brain. Brains from male mice were isolated at 3-32 months of age. Pyrosequencing analyses revealed significantly increased Ogg1 methylation with ageing, which correlated inversely with Ogg1 expression. The reduced Ogg1 expression correlated with enhanced expression of methyl-CpG binding protein 2 and ten-eleven translocation enzyme 2. A significant inverse correlation between Neil1 methylation at CpG-site2 and expression was also observed. BER activity was significantly reduced and associated with increased 8-oxo-7,8-dihydro-2'-deoxyguanosine levels. These data indicate that Ogg1 and Neil1 expression can be epigenetically regulated, which may mediate the effects of ageing on DNA repair in the brain.

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Genes, 8, , , 2017

PMID: 28218666

Genome-wide base-resolution mapping of DNA methylation in single cells using single-cell bisulfite sequencing (scBS-seq).
Clark SJ, Smallwood SA, Lee HJ, Krueger F, Reik W, Kelsey G

DNA methylation (DNAme) is an important epigenetic mark in diverse species. Our current understanding of DNAme is based on measurements from bulk cell samples, which obscures intercellular differences and prevents analyses of rare cell types. Thus, the ability to measure DNAme in single cells has the potential to make important contributions to the understanding of several key biological processes, such as embryonic development, disease progression and aging. We have recently reported a method for generating genome-wide DNAme maps from single cells, using single-cell bisulfite sequencing (scBS-seq), allowing the quantitative measurement of DNAme at up to 50% of CpG dinucleotides throughout the mouse genome. Here we present a detailed protocol for scBS-seq that includes our most recent developments to optimize recovery of CpGs, mapping efficiency and success rate; reduce hands-on time; and increase sample throughput with the option of using an automated liquid handler. We provide step-by-step instructions for each stage of the method, comprising cell lysis and bisulfite (BS) conversion, preamplification and adaptor tagging, library amplification, sequencing and, lastly, alignment and methylation calling. An individual with relevant molecular biology expertise can complete library preparation within 3 d. Subsequent computational steps require 1-3 d for someone with bioinformatics expertise.

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Nature protocols, 12, 1750-2799, 534-547, 2017

PMID: 28182018

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Latest Publications

DNA methylation homeostasis in human and mouse development.

Iurlaro M, von Meyenn F, Reik W

Current opinion in genetics & development
43 1879-0380:101-109 (2017)

PMID: 28260631

The Ageing Brain: Effects on DNA Repair and DNA Methylation in Mice.

Langie SA, Cameron KM, Ficz G

Genes
8 : (2017)

PMID: 28218666

Tracking the embryonic stem cell transition from ground state pluripotency.

Kalkan T, Olova N, Roode M

Development (Cambridge, England)
1477-9129: (2017)

PMID: 28174249

Gender Differences in Global but Not Targeted Demethylation in iPSC Reprogramming.

Milagre I, Stubbs TM, King MR

Cell reports
18 2211-1247:1079-1089 (2017)

PMID: 28147265

A Hox-Embedded Long Noncoding RNA: Is It All Hot Air?

Selleri L, Bartolomei MS, Bickmore WA

PLoS genetics
12 1553-7404:e1006485 (2016)

PMID: 27977680

Efficient targeted DNA methylation with chimeric dCas9-Dnmt3a-Dnmt3L methyltransferase.

Stepper P, Kungulovski G, Jurkowska RZ

Nucleic acids research
1362-4962: (2016)

PMID: 27899645

The H3K9 dimethyltransferases EHMT1/2 protect against pathological cardiac hypertrophy.

Thienpont B, Aronsen JM, Robinson EL

The Journal of clinical investigation
1558-8238: (2016)

PMID: 27893464

Retinol and ascorbate drive erasure of epigenetic memory and enhance reprogramming to naïve pluripotency by complementary mechanisms.

Hore TA, von Meyenn F, Ravichandran M

Proceedings of the National Academy of Sciences of the United States of America
1091-6490: (2016)

PMID: 27729528

Comparative Principles of DNA Methylation Reprogramming during Human and Mouse In Vitro Primordial Germ Cell Specification.

von Meyenn F, Berrens RV, Andrews S

Developmental cell
39 1878-1551:104-115 (2016)

PMID: 27728778

MERVL/Zscan4 Network Activation Results in Transient Genome-wide DNA Demethylation of mESCs.

Eckersley-Maslin MA, Svensson V, Krueger C

Cell reports
17 2211-1247:179-92 (2016)

PMID: 27681430

In vivo genome-wide profiling reveals a tissue-specific role for 5-formylcytosine.

Iurlaro M, McInroy GR, Burgess HE

Genome biology
17 1474-760X:141 (2016)

PMID: 27356509