Epigenetics

  • Article |

    Epigenetic changes during the differentiation of bone-resorbing cells have important implications in bone remodelling. Here the authors target this pathway with I-BET151, an inhibitor of bromo and extra-terminal proteins that inhibits expression of the MYC-NFAT axis and suppresses bone loss in multiple mouse models.

    • Kyung-Hyun Park-Min
    • , Elisha Lim
    •  & Lionel B Ivashkiv
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    Reduced expression of DICER—responsible for the processing of microRNA precursors—was previously linked to poor clinical outcomes in cancer patients. Here, the authors uncover an epigenetic mechanism by which hypoxia suppresses DICER expression and deregulates the miR-200-Zeb1 circuit in breast cancer to promote the tumour phenotype.

    • Twan van den Beucken
    • , Elizabeth Koch
    •  & Bradly G. Wouters
  • Article
    | Open Access

    DNA methylation is essential for proper gene expression, development and genome stability. Here the authors present whole-genome DNA methylation analyses of purified mouse cardiomyocytes from newborn, adult and failing hearts and find highly dynamic patterns between the three phenotypes of cardiomyocytes.

    • Ralf Gilsbach
    • , Sebastian Preissl
    •  & Lutz Hein
  • Article |

    Extreme fetal growth is associated with increased risk of various adult diseases, although the mechanism underlying these associations is poorly understood. Here the authors show that abnormal fetal growth correlates with increased DNA methylation levels and report sex-specific epigenetic patterns associated with fetal growth.

    • Fabien Delahaye
    • , N. Ari Wijetunga
    •  & Francine H. Einstein
  • Article
    | Open Access

    Pneumococci can alternate between harmless and highly virulent forms. Here the authors show that such variation may be due to random rearrangements in a genetic locus encoding a restriction-modification system, resulting in epigenetic changes that affect expression of many genes.

    • Ana Sousa Manso
    • , Melissa H. Chai
    •  & Marco R. Oggioni
  • Article |

    X-chromosome inactivation is a tightly regulated mechanism, which silences one of the two female X chromosomes. Here Makhlouf et al. show that the autosomal transcription factor YY1 directly promotes expression of the XistRNA—a master regulator of X-chromosome inactivation—at the onset of the inactivation process.

    • Mélanie Makhlouf
    • , Jean-François Ouimette
    •  & Claire Rougeulle
  • Article
    | Open Access

    Chronic infection with the bacterium Helicobacter pylori is associated with inflammation and increased risk of gastric cancer. Kiga et al. show that methylation and silencing of the microRNA gene miR-210is associated with infection in humans, and promotes proliferation of gastric epithelial cells in culture.

    • Kotaro Kiga
    • , Hitomi Mimuro
    •  & Chihiro Sasakawa
  • Article |

    The process that balances expression of X-chromosomal genes between males and females is under tight regulatory control. Here, Militti et al. show that in Drosophila, the RNA-binding protein UNR functions during dosage compensation to promote the interaction between the RNA helicase MLE and the long non-coding RNA roX2.

    • Cristina Militti
    • , Sylvain Maenner
    •  & Fátima Gebauer
  • Article
    | Open Access

    Changes in chromatin structure impact gene expression programs by modulating accessibility to the transcription machinery. Here, West et al. explore differences in nucleosome occupancy between mammalian pluripotent and somatic cells and uncover regulatory regions likely to play key roles in determining cell identity.

    • Jason A. West
    • , April Cook
    •  & Robert E. Kingston
  • Article |

    The onset of flowering is a major developmental transition in plants. Here, Hou et al. show that a NF-Y transcription factor complex exerts epigenetic control over the timing of flowering in Arabidopsisby modulating trimethylated H3K27 levels at a floral pathway integrator, SOC1, in response to environmental and intrinsic signals.

    • Xingliang Hou
    • , Jiannan Zhou
    •  & Hao Yu
  • Article |

    Imprinted mouse X-chromosome inactivation is controlled by two long non-coding RNAs, Tsix and Xist. Here, Maclary et al. demonstrate that Tsix is dispensable during the initiation and maintenance of X-inactivation in vivo and in vitro, but required to prevent Xist expression as trophectodermal progenitors differentiate.

    • Emily Maclary
    • , Emily Buttigieg
    •  & Sundeep Kalantry
  • Article |

    Selecting for varieties of commercial crops with enhanced nutritional quality is important in agriculture. Here, the authors identify alleles of a gene in tomatoes that give rise to increased levels of vitamin E and find that the promoter of the gene is differentially methylated.

    • Leandro Quadrana
    • , Juliana Almeida
    •  & Fernando Carrari
  • 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