Epigenetics

  • Article
    | Open Access

    Peptidylarginine deiminase 4 (PADI4) is a transcriptional co-regulator that converts arginine residues at histone tails to citrulline. The authors show that PADI4 interacts with the central haematopoietic transcription factor TAL1 to regulate gene expression in an erythroleukemia cell line.

    • Stephan Kolodziej
    • , Olga N. Kuvardina
    •  & Jörn Lausen
  • Article
    | Open Access

    Maternal diet affects DNA methylation in the developing offspring, leading to phenotypic changes. Here, Dominguez-Salas et al. exploit seasonal variation in the diet of Gambian women to show that maternal methyl donor nutrient status around the time of conception predicts methylation levels at metastable epialleles in infants.

    • Paula Dominguez-Salas
    • , Sophie E. Moore
    •  & Branwen J. Hennig
  • Article
    | Open Access

    Defective proteins or functional proteins that are no longer needed can be degraded in the endoplasmic reticulum. In this study, Lopez-Serra et al.show that DERL3, which is involved in protein degradation in the endoplasmic reticulum, is aberrantly silenced in cancer, leading to activation of a glucose transporter and dysregulated glycolysis.

    • Paula Lopez-Serra
    • , Miguel Marcilla
    •  & Manel Esteller
  • Article |

    Epigenetic codes translate external stimuli into targeted and long-lasting gene regulation. In this study, the authors show that regenerative retrograde signalling activates the epigenetic modifying enzyme PCAF, inducing gene expression and promoting axon regeneration in a mouse spinal cord injury model.

    • Radhika Puttagunta
    • , Andrea Tedeschi
    •  & Simone Di Giovanni
  • Article
    | Open Access

    CD8 expression levels on peripheral CD8+ T cells are regulated during development and effector differentiation. Here, the authors show that methylation patterns at the Cd8a locus, whose product is essential for surface CD8 expression, can change during T-cell development, activation, cytokine polarization and reprogramming.

    • Kim L. Harland
    • , E. Bridie Day
    •  & Anne Kelso
  • Article
    | Open Access

    Genetically identical twins provide a valuable resource to identify epigenetic factors associated with complex traits. Here the authors adopt this approach and find that differential methylation of the pain gene TRPA1is associated with pain sensitivity in humans.

    • J.T. Bell
    • , A.K. Loomis
    •  & T.D. Spector
  • Article |

    Polycomb group proteins are epigenetic gene silencers that are thought to exist in two biochemically distinct multiprotein complexes, termed PRC-1 and -2. Here, Cao et al.show that EED, a core component of PRC2, interacts with and functions as part of PRC1, thus coordinating the activities of both complexes.

    • Qi Cao
    • , Xiaoju Wang
    •  & Arul M. Chinnaiyan
  • Article |

    The Hoppel transposable element mediates heterochromatin formation in Drosophila. Here Savva et al. report that the RNA-editing enzyme, ADAR, edits a long double-stranded RNA generated by the Hoppeltransposon, thereby regulating heterochromatin formation and gene expression.

    • Yiannis A. Savva
    • , James E. C. Jepson
    •  & Robert A. Reenan
  • Article |

    The miR-372-3 cluster has a role in oncogenesis. In this study, by utilizing parthenogenetic induced pluripotent stem cells, that lack the paternal genome, Stelzer et al.report that these miR-372-3 are negatively regulated by a paternally imprinted antisense transcript and that loss of its expression promotes oncogenesis.

    • Yonatan Stelzer
    • , Ido Sagi
    •  & Nissim Benvenisty
  • Article |

    Semiconductor-based, non-optical DNA sequencing technologies such as Ion Torrent sequencing offer speed and cost advantages compared with alternative techniques. Cheng et al. demonstrate a protocol allowing the use of Ion Torrent technology to sequence DNA from chromatin immunoprecipitation experiments.

    • Christine S. Cheng
    • , Kunal Rai
    •  & Ido Amit
  • Article |

    H3K64 trimethylation on the nucleosome lateral surface marks pericentric heterochromatin. Here Lange et al.show that H3K64me3 enrichment ensures heterochromatin integrity and occurs in an H3K9me3-dependent, but an H4K20me3- and heterochromatin protein 1-independent manner.

    • Ulrike C. Lange
    • , Stéphanie Siebert
    •  & Robert Schneider
  • Article |

    Chemical modifications of CpG dinucleotides form part of the epigenetic code and various methods for the detection of modified CpG sites exist. Here Kriukiene and colleagues report a complementary method that allows the profiling of unmodified CpG sites within the genome, which they call the 'unmethylome'.

    • Edita Kriukienė
    • , Viviane Labrie
    •  & Saulius Klimašauskas
  • Article |

    Changes in DNA methylation during mammalian spermatogenesis are poorly understood. The authors show that the content of 5-hydroxymethylcytosine, a stable intermediate of DNA demethylation, changes dynamically during mouse spermatogenesis and is associated with functional genomic regions and transcription.

    • Haiyun Gan
    • , Lu Wen
    •  & Fuchou Tang
  • Article |

    Even though both embryonic stem cells and primordial germ cells express pluripotency markers, they differ in their developmental potential. Maeda et al. show that, in embryonic stem cells, the Myc family member Max mediates epigenetic repression of genes involved in germ cell development.

    • Ikuma Maeda
    • , Daiji Okamura
    •  & Yasuhisa Matsui
  • Article |

    Epigenetic inheritance of DNA methylation requires the recruitment of DNA methyltransferase activity to the replication fork by UHRF1. Liu et al. show that optimal association of UHRF1 with the replication fork and resulting DNA methylation requires two domains that bind hemi-methylated DNA and methylated histones, respectively.

    • Xiaoli Liu
    • , Qinqin Gao
    •  & Jiemin Wong
  • Article
    | Open Access

    The factors that modulate growth rate of the human malaria parasite Plasmodium falciparum remain poorly understood. Here Scherf and collaborators demonstrate that the Plasmodiumsirtuin PfSir2a regulates the transcription of ribosomal DNA, thereby modulating parasite proliferation rate and virulence.

    • Liliana Mancio-Silva
    • , Jose Juan Lopez-Rubio
    •  & Artur Scherf
  • Article
    | Open Access

    Plant pathogens encode effector proteins that trigger immunity in plants carrying appropriate resistance genes. Here Qutob et al. show non-Mendelian interactions between naturally occurring Phytophthora sojaealleles that result in transgenerational gene silencing and gain of virulence in soybean plants.

    • Dinah Qutob
    • , B. Patrick Chapman
    •  & Mark Gijzen
  • Article
    | Open Access

    Environmental factors can influence one's susceptibility to cancer, but it is not clear whether such an influence extends beyond the directly exposed generations. Here, feeding pregnant rats with a high-fat diet or a hormone derivative, the authors observe increased breast cancer risk in up to three subsequent generations.

    • Sonia de Assis
    • , Anni Warri
    •  & Leena Hilakivi-Clarke
  • Article |

    Chromatin in embryonic stem cells is present in an open state presumably to facilitate gene expression changes required for pluripotency and subsequent multilineage differentiation. This study describes roles for lamin A, histone acetylation and G9a-mediated histone H3 lysine 9 methylation in regulating chromatin plasticity in these cells.

    • Shai Melcer
    • , Hadas Hezroni
    •  & Eran Meshorer
  • Article |

    Epigenetic and genetic factors have a role in obesity but the role of epigenetics in this disease is unclear. Here, Liet al. investigated global DNA methylation patterns in three breeds of pigs that have different fat contents, providing a resource for the further analysis of differentially methylated gene promoters in obesity.

    • Mingzhou Li
    • , Honglong Wu
    •  & Ruiqiang Li
  • Article |

    Hox gene expression is induced upon cellular differentiation and is inhibited in pluripotent cells. Bocker and colleagues show that the maintenance of induced transcription depends on Tet2 mediated hydroxylation of 5-methylcytosine at theHoxagene locus, indicating that this epigenetic switch is required for an active chromatin state and gene expression.

    • Michael T. Bocker
    • , Francesca Tuorto
    •  & Achim Breiling
  • Article
    | Open Access

    Lysine-specific demethylase 1 (LSD1) removes methyl groups from mono-methylated and dimethylated lysine 4 of histone H3 and represses transcription. In this study, a role for LSD1 in the regulation of genes involved in energy expenditure in adipocytes is reportedin vitroand in mice fed on a high-fat diet.

    • Shinjiro Hino
    • , Akihisa Sakamoto
    •  & Mitsuyoshi Nakao
  • Article |

    Chromatin is rendered silent by epigenetic marks when in proximity to telomeres, and, in yeast, this effect requires the histone-modifying enzyme Sir2. In this study, the human Sir2 family member SIRT6 is shown to modulate the telomere position effect in human cells.

    • Ruth I. Tennen
    • , Dennis J. Bua
    •  & Katrin F. Chua
  • Article
    | Open Access

    The chronic disease schistosomiasis is caused by the blood flukeSchistosoma mansoni. By studying DNA modifications throughout the lifecycle of the pathogen, the authors identify DNA methylation as a factor in egg development and suggest that the epigenetic machinery responsible may be a therapeutic target.

    • Kathrin K. Geyer
    • , Carlos M. Rodríguez López
    •  & Karl F. Hoffmann
  • Article
    | Open Access

    Polo-like kinase 1 is a key regulator of mitosis and is a candidate for drug development to treat cancer. Here, reduced expression of polo-like kinase 1 in adult mice has a minor impact on animal physiology, suggesting that polo-like kinase 1 inhibitors may be useful in the killing of tumour cells while sparing normal cells.

    • Monika Raab
    • , Sven Kappel
    •  & Klaus Strebhardt
  • Article |

    Pronucleus DNA becomes demethylated during zygotic development. Here, the authors demonstrate that the reduction in 5-methylcytosine levels is accompanied by an increase in the presence of 5-hydroxymethylcytosine, and suggest that this has a role in developmental reprogramming.

    • Mark Wossidlo
    • , Toshinobu Nakamura
    •  & Jörn Walter
  • Article
    | Open Access

    How one copy of the X chromosome is silenced in replicating female somatic cells is poorly understood. Here, the authors demonstrate that the inactive X chromosome is replicated before constitutive heterochromatin and that histone hypoacetylation has a role in controlling replication of the inactive X chromosome.

    • Corella S. Casas-Delucchi
    • , Alessandro Brero
    •  & M. Cristina Cardoso
  • Article |

    Pseudogenes are prevalent in the human genome; however, their biological function is relatively unknown. In this study, the high mobility group A1 (HMGA1) pseudogene is shown to destabilizeHMGA1 mRNA. These findings have implications for diabetes, as two patients are reported to express high levels of the HMGA1pseudogene.

    • Eusebio Chiefari
    • , Stefania Iiritano
    •  & Antonio Brunetti