Cover image for Vol. 38 Issue 10

Edited By: Andrew Moore

Online ISSN: 1521-1878



Find below our most recent articles on a variety of aspects of epigenetics, from chromatin organisation to the role of epigenetics in cancer. This collection sheds light on, and raises new questions on the role of chemical modifications of DNA and chromatin, and non-coding RNAs, in modulating gene expression in a variety of processes from development to cancer. We hope you enjoy delving into this concentration of most recent thinking, insights and future perspectives in epigenetics.

BioEssays is affiliated with EpiGeneSys, the European Network of Excellence for epigenetics research.Epigenesys_logo

For primer literature related to the contents below, see also the Encyclopedia of Life SciencesELS_Logoentry Epigenetics and Disease.

Take a look at this lecture by EpiGeneSys member Leonie Ringrose on Epigenetics: myths, mysteries and molecule.
A larger version of this video can be found here.

Adenine methylation in eukaryotes: Apprehending the complex evolutionary history and functional potential of an epigenetic modification
Lakshminarayan M. Iyer, Dapeng Zhang and L. Aravind, BioEssays, Volume 38, Issue 1, January 2016, in press.

adenine methylation, chromatin, dioxygenases, methyltransferases, modified DNA, restriction modification, transcription regulation

Recent studies have brought to fore the importance of DNA adenine methylation as a potential epigenetic mark across phylogenetically distant eukaryotes. We synthesize the current understanding of the manifold origins, biochemistry, and biology of the addition, removal, and reading of this epigenetic mark.

Also watch the accompanying Video Abstract.

N6-methyladenine functions as a potential epigenetic mark in eukaryotes
Qinmiao Sun, Shoujun Huang, Xiaona Wang, Yuanxiang Zhu, Zhenping Chen and Dahua Chen, BioEssays, Volume 37, Issue 11, November 2015, pages 1155-1162.

DNA methylation, epigenetic control, eukaryotes, gene regulation, N6-methyladenine, 5-methylcytosine

Like 5mC, 6mA functions as a potential epigenetic mark in higher eukaryotes. The expression of target genes can be modulated via dynamic and reversible pattern of DNA methylation in a variety of biological processes.

H2A.Z helps genes remember their history so we can remember ours
Iva B. Zovkic and Brandon J. Walters, BioEssays, Volume 37, Issue 6, June 2015, pages 596–601.

H2A.Z, histone subunit exchange, histone variant exchange, learning, memory, poised genes, transcriptional memory

Poised promoters, maintained by histone H2A.Z incorporation into nucleosomes, allow genes to respond to future stimuli based on the history of prior activity. Based on our recent discovery of H2A.Z function in learning and memory, we speculate that stable H2A.Z incorporation supports long-term memory maintenance by promoting re-activation of memory-promoting genes.

Multiple dimensions of epigenetic gene regulation in the malaria parasite Plasmodium falciparum
Ferhat Ay, Evelien M. Bunnik, Nelle Varoquaux, Jean-Philippe Vert, William Stafford Noble and Karine G. Le Roch, BioEssays, Volume 37, Issue 2, February 2015, pages 182-194.

epigenetics, gene regulation, histone modifications, malaria, nucleosome occupancy, three-dimensional genome organization, virulence genes

The malaria parasite Plasmodium falciparum actively regulates a large fraction of its genes throughout its replicative cycle inside human red blood cells. Recent studies show epigenetic factors such as changes in histone modifications, nucleosome occupancy and the three-dimensional genome structure play an important role in this precise gene regulation.

Do age-associated DNA methylation changes increase the risk of malignant transformation?
Wolfgang Wagner, Carola I. Weidner and Qiong Lin, BioEssays, Volume 37, Issue 1, January 2015, pages 20-24.

aging, cancer, DNA-methylation, DNMT3A, epigenetic, epimutation, predictor

DNA damage has since long been suspected to be a major cause of aging. Here, I will discuss the dual role of genome maintenance systems in providing DNA sequence variation in the germline as the substrate for evolution and mediating DNA damage-induced aging phenotypes in the soma.

Now you see it: Genome methylation makes a comeback in Drosophila
Dario Boffelli, Sachiko Takayama and David I. K. Martin, BioEssays, Volume 36, Issue 12, December 2014, pages 1138-1144.

development, Drosophila, methylation

Methylcytosine immunoprecipitation and deep sequencing reveal a strand-asymmetric pattern of cytosine methylation in the fly genome (top). Short regions (middle) contain methylcytosine in non-CpG sequence motifs (bottom). The regions are methylated in only a fraction of fly genomes; specific regions might be methylated in distinct subsets of embryonic nuclei (right).

Early life epigenetic programming and transmission of stress-induced traits in mammals
Katharina Gapp, Lukas von Ziegler, Ry Yves Tweedie-Cullen and Isabelle M. Mansuy, BioEssays, Volume 36, Issue 5, May 2014, pages 491-502.
DOI: 10.1002/bies.201300116

acquired traits, early life stress, epigenetic inheritance

Evidence for epigenetic inheritance of acquired traits in mammals is growing. Transgenerational transmission is based on mechanisms involving DNA-methylation, histone post-translational modifications, and non-coding small RNAs in the germline. These epigenetic modifications constitute potential vehicles for effects of early life stress and nutrition on brain and behavior across generations.

Epigenetic programing of depression during gestation
Stephanie C. Dulawa, BioEssays, Volume 36, Issue 4, April 2014, pages 353-358.
DOI: 10.1002/bies.201300089

animal model, chromatin remodeling, depression, development, methylation, mood disorder, prenatal

How does the gestational environment transduce vulnerability to depression to the fetus? The in utero environment alters gene expression through epigenetic mechanisms, which mediate long-term effects on physiology and behavior without changing DNA sequence. I examine recent work suggesting that gestational environment programs depression in adult offspring via epigenetics.

A paternal environmental legacy: Evidence for epigenetic inheritance through the male germ line
Adelheid Soubry, Cathrine Hoyo, Randy L. Jirtle and Susan K. Murphy, BioEssays, Volume 36, Issue 4, April 2014, pages 359-371.
DOI: 10.1002/bies.201300113

developmentaly origins of health and disease (DOHaD), environment, epigenetics, imprinted genes, offspring, paternal exposures, spermatogenesis, transgenerational effects

Animal and epidemiologic studies on various environmental exposures suggest that transgenerational epigenetic changes can be induced through the paternal germ line, ultimately affecting health status of the offspring. This essay suggests the existence of epigenetic windows of susceptibility to environmental insults during spermatogenesis or other early developmental processes.

DNA methylation reprogramming in cancer: Does it act by re-configuring the binding landscape of Polycomb repressive complexes?
James P. Reddington, Duncan Sproul and Richard Meehan, BioEssays, Volume 36, Issue 2, February 2014, pages 134-140.
DOI: 10.1002/bies.201300130

cancer epigenetics, DNA methylation, epigenomics, H3K27me3, Polycomb, reprogramming

DNA methylation patterns are subject to widespread reprogramming during cancer development, the implications of which for the regulation of the cancer genome are not fully understood. Here we discuss how DNA methylation reprogramming could influence transcriptional regulation in cancer cells by modifying the genome-wide targeting of the Polycomb repression system.

Unmasking risk loci: DNA methylation illuminates the biology of cancer predisposition
Dvir Aran and Asaf Hellman, BioEssays, Volume 36, Issue 2, February 2014, pages 184-190.
DOI: 10.1002/bies.201300119

cancer, common human disease, disease risk loci, DNA methylation, epigenomics, gene regulation, transcriptional enhancers

Tumor samples exhibit genetic and epigenetic variations across individuals. However, cancer-associated risk sequence alleles failed to reveal the link with the mechanism of cancer (left). Implementation of DNA methylation data helps to resolve the effect on drivers of cancer development, and hence to explains the biology of cancer susceptibility (right).

Integrating DNA methylation dynamics into a framework for understanding epigenetic codes
Keith E. Szulwach and Peng Jin, BioEssays, Volume 36, Issue 1, January 2014, pages 107-117.
DOI: 10.1002/bies.201300090

chromatin, DNA demethylation, DNA methylation, epigenetics

DNA methylation regulates gene expression and influences cellular phenotypes, thereby encoding information on the genome. Recently it has been appreciated that DNA methylation may be dynamically regulated. This essay discusses the integration of DNA methylation into epigenetic codes, summarizing paradigm shifts related to the dynamic encoding of epigenetic information.

Homosexuality via canalized sexual development: A testing protocol for a new epigenetic model
William R. Rice, Urban Friberg and Sergey Gavrilets, BioEssays, Volume 35, Issue 9, September 2013, pages 764-770.
DOI: 10.1002/bies.201300033

epigenetics, gonad-trait discordance, homosexuality

We recently advanced a new biological model of homosexuality that is based on transgenerational inheritance of sex-specific epigenetic marks from a parent to an offspring of opposite sex. Here, we describe a general framework to test the model using human stem cells from adult hetero- and homosexual individuals.

How epigenetic mutations can affect genetic evolution: Model and mechanism
Filippos D. Klironomos, Johannes Berg and Sinéad Collins, BioEssays, Volume 35, Issue 6, June 2013, pages 571-578.
DOI: 10.1002/bies.201200169

adaptive walks, epigenetics, methylation, non-genetic inheritance

Heritable epigenetic mutations have higher mutation and reversion rates than genetic mutations, but can still be acted on by natural selection. We use a model to show why pure epigenetic variation can speed up adaptation and lead to phenotype-first evolution, even on time scales where genetic evolution also happens.

Is adult stem cell aging driven by conflicting modes of chromatin remodeling?
Jens Przybilla, Joerg Galle and Thimo Rohlf, BioEssays, Volume 34, Issue 10, October 2012, pages 841-848.
DOI: 10.1002/bies.201100190

age-related changes of chromatin structure, DNA-methylation, histone modification, inheritance of epigenetic information, stem cell plasticity

We hypothesize that age-related changes of chromatin structure originate in the limited cellular capability to inherit epigenetic information. Spontaneous loss of histone modification, e.g., during replication gives rise to changes in DNA methylation and accordingly in gene expression, manifesting a conflict between stem cell plasticity and long term gene silencing.

Epigenetics meets mathematics: Towards a quantitative understanding of chromatin biology
Philipp A. Steffen, Joao P. Fonseca and Leonie Ringrose, BioEssays, Volume 34, Issue 10, October 2012, pages 901-913.
DOI: 10.1002/bies.201200076

chromatin, epigenetics, mathematical modelling, quantification, rate constants

Current models for chromatin mediated gene regulation often describe molecules as binding, modifying or recruiting other molecules, but with little reference to the quantitative differences between them. In this review we explore how quantitative and mathematical approaches can give insights into mechanisms of epigenetic regulation.

Longevity and the long arm of epigenetics: Acquired parental marks influence lifespan across several generations
Shanshan Pang and Sean P. Curran, BioEssays, Volume 34, Issue 8, August 2012, pages 652-654.
DOI: 10.1002/bies.201200046

epigenetics, lifespan, longevity, parental marks

A recent study reported that longevity in Caenorhabditits elegans can be inherited over several generations. This is probably achieved through the following epigenetic mechanism: inherited demethylated histones at some central loci, such as miRNA, transcription factors or signaling regulators affect the expression of certain genes leading to the longevity phenotype.

Please also read the following articles from the Encyclopedia of Molecular Cell Biology and Molecular Medicine:


Epigenetic Medicine

Molecular Genetics of Genome Imprinting

The Human Epigenome