Epigenetics articles within Nature Communications

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  • Article
    | Open Access

    Active and passive demethylation pathways have been implicated in the genome-wide erasure of 5mC accompanying mammalian preimplantation development. Here the authors reveal a recently evolved, mammalian-specific pathway in which global hypomethylation is achieved by the coupling of active and passive demethylation.

    • Christopher B. Mulholland
    • , Atsuya Nishiyama
    •  & Heinrich Leonhardt

  • Article
    | Open Access

    Hepatic lipogenesis is a tightly regulated process, which is elevated in obesity. Here the authors report that FGF15/19, bile acid-induced gut hormones, repress lipogenic genes in the late fed-state by activating small heterodimer partner (SHP) and promoting SHP-dependent recruitment of DNA methyltransferase DNMT3A to lipogenic genes.

    • Young-Chae Kim
    • , Sunmi Seok
    •  & Jongsook Kim Kemper

  • Review Article
    | Open Access

    Histone H2A monoubiquitination on lysine 119 in vertebrate and lysine 118 in Drosophila (H2Aub) is an epigenomic mark usually associated with gene repression by Polycomb group factors. Here the authors review the current knowledge on the deposition and removal of H2Aub, its function in transcription and other DNA-associated processes as well as its relevance to human disease.

    • Haithem Barbour
    • , Salima Daou
    •  & El Bachir Affar

  • Article
    | Open Access

    Epigenetically altered genes can have a key role in cancer pathobiology but epigenetic signatures that distinguish oncogenes are not yet known. Here, the authors identify broad genic repression domains, defined by widespread H3K27me3 modification, as an epigenetic signature to provide mutation-independent information for discovery of potential oncogenes.

    • Dongyu Zhao
    • , Lili Zhang
    •  & Kaifu Chen

  • Article
    | Open Access

    The paternal genome in mice undergoes widespread DNA methylation loss post-fertilization. Here, the authors apply allele-specific analysis of WGBS data to show that a number of genomic regions are simultaneously de novo methylated on the paternal genome dependent on maternal DNMT3A activity, which induces transcriptional silencing of this allele in the early embryo.

    • Julien Richard Albert
    • , Wan Kin Au Yeung
    •  & Matthew Lorincz

  • Article
    | Open Access

    The histone variant mutation H3.3-G34W occurs in the majority of giant cell tumor of bone (GCTB). By profiling patient-derived GCTB tumor cells, the authors show that this mutation associates with epigenetic alterations in heterochromatic and bivalent regions that contribute to an impaired osteogenic differentiation and the osteolytic phenotype of GCTB.

    • Pavlo Lutsik
    • , Annika Baude
    •  & Christoph Plass

  • Article
    | Open Access

    The meiotic transmissibility and progeny phenotypic influence of graft-mediated epigenetic changes remain unclear. Here, the authors use the msh1 mutant in the rootstock to trigger heritable enhanced growth vigor in Arabidopsis and tomato, and show it is associated with the RNA-directed DNA methylation pathway.

    • Hardik Kundariya
    • , Xiaodong Yang
    •  & Sally A. Mackenzie

  • Article
    | Open Access

    Allele-specific measurements can reveal differences in DNA methylation between homologous alleles associated with changes in genetic sequence. Here, the authors develop a method for detecting allele specific methylation events within haplotypes of linked SNPs, compare it with existing methods, and show it identifies haplotypes for which the genetic variant carries significant information about the methylation state of the allele of origin.

    • J. Abante
    • , Y. Fang
    •  & J. Goutsias

  • Article
    | Open Access

    Previous work suggested that histone demethylase JMJD3 is detrimental to somatic cell reprogramming. Here, the authors show that while JMJD3 has a context-independent detrimental effect on early stages of reprogramming, during late stages it activates epithelial and pluripotency genes together with Klf4.

    • Yinghua Huang
    • , Hui Zhang
    •  & Baoming Qin

  • Article
    | Open Access

    Chromatin state underlies cellular function, and transcription factor binding patterns along with epigenetic marks define chromatin state. Here the authors show that the histone chaperone ANP32E functions through regulation of H2A.Z to restrict genome-wide chromatin accessibility and to inhibit gene transcriptional activation.

    • Kristin E. Murphy
    • , Fanju W. Meng
    •  & Patrick J. Murphy

  • Article
    | Open Access

    The HUSH complex plays a key role in controlling transcription of viruses and transposable elements. Here, the authors define the biochemical basis of HUSH assembly and show that the TASOR subunit contains a pseudo-PARP domain critical for HUSH-dependent transgene repression and H3K9me3 deposition over targets genome wide.

    • Christopher H. Douse
    • , Iva A. Tchasovnikarova
    •  & Yorgo Modis

  • Article
    | Open Access

    Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions with repetitive and restrictive behaviours. Here the authors integrate mRNA expression, miRNA expression, DNA methylation, and histone acetylation datasets from a collection of post mortem brain tissues and identify a convergent molecular subtype of ASD.

    • Gokul Ramaswami
    • , Hyejung Won
    •  & Daniel H. Geschwind

  • Article
    | Open Access

    Polycomb (PcG) and Trithorax (TrxG) group regulate several hundred target genes with important roles in development and disease. Here the authors combine experiment and theory to provide evidence that the Polycomb/Trithorax system has the potential for a rich repertoire of regulatory modes beyond simple epigenetic memory.

    • Jeannette Reinig
    • , Frank Ruge
    •  & Leonie Ringrose

  • Article
    | Open Access

    Preimplantation embryos undergo extensive transcriptomic and epigenomic remodeling. Here the authors assay open chromatin in bovine oocytes, embryos, and embryonic stem cells, and compare the transcriptomes and epigenomes of cattle, human and mouse embryos, revealing species-specific regulation of genome activation.

    • Michelle M. Halstead
    • , Xin Ma
    •  & Pablo J. Ross

  • Article
    | Open Access

    Mutations in RAS-MAPK pathway genes are implicated in Noonan-spectrum, yet up to 20% of cases have unknown cause. Here, the authors identify RREB1 underlying a 6p microdeletion RASopathy-like syndrome and show that RREB1, SIN3A and KDM1A form a transcriptional repressive complex to control methylation of MAPK pathway genes.

    • Oliver A. Kent
    • , Manipa Saha
    •  & Robert Rottapel

  • Article
    | Open Access

    Epigenetic mechanisms have emerged as contributors to the molecular impairments caused by exposure to environmental factors such as abused substances. Here the authors perform epigenetic profiling of the striatum and identify the tyrosine kinase FYN is an important driver of neurodegenerative-like pathology and drug-taking behaviour.

    • Gabor Egervari
    • , Diana Akpoyibo
    •  & Yasmin L. Hurd

  • Article
    | Open Access

    Although Huntington’s disease (HD) is a well-studied genetic disorder, less is known about the epigenetic changes underlying it. Here, the authors characterize DNA methylation levels in tissues from patients, a mouse huntingtin (Htt) gene knock-in model, and a transgenic HTT sheep model, and provide evidence that HD is accompanied by DNA methylation changes in these three species.

    • Ake T. Lu
    • , Pritika Narayan
    •  & Steve Horvath

  • Article
    | Open Access

    Evidence for transgenerational inheritance of epigenetic information in vertebrates is scarce. Here the authors report that homozygous dnmt1 mutant zebrafish are essentially normal, with the exception of impaired lymphopoiesis, with impaired larval (but not adult) T cell development being transmitted to subsequent generations by genotypically wildtype fish.

    • Norimasa Iwanami
    • , Divine-Fondzenyuy Lawir
    •  & Thomas Boehm

  • Article
    | Open Access

    S. cerevisiae TBP associated factor 14 (Taf14) is a transcriptional regulator that interacts with multiple nuclear complexes. Here, the authors report that the extra-terminal domain of Taf14 (Taf14ET) recognizes a common motif in various transcriptional coactivator proteins and they solve the NMR structure of Taf14ET bound the ET-binding motif of Sth1, the catalytic subunit of the RSC (Remodel the Structure of Chromatin) complex, and furthermore show that Taf14ET undergoes liquid-liquid phase separation, which is enhanced by Taf14 interaction partners.

    • Guochao Chen
    • , Duo Wang
    •  & Yong Chen

  • Article
    | Open Access

    Genetic variants in KIF3A are associated with atopic dermatitis (AD). Here, the authors identify two AD-risk alleles that show high methylation resulting in lower KIF3A expression. Mice with epidermis-specific loss of Kif3a show disrupted skin barrier homeostasis and increased AD susceptibility.

    • Mariana L. Stevens
    • , Zhonghua Zhang
    •  & Gurjit K. Khurana Hershey

  • Article
    | Open Access

    Reconstructing the early molecular evolution of animals requires genomic resources for non-bilaterian animals. Here, the authors present the chromosome-level genome of a freshwater sponge together with analyses of its genome architecture, methylation, developmental gene expression, and microbiome.

    • Nathan J. Kenny
    • , Warren R. Francis
    •  & Sally P. Leys

  • Article
    | Open Access

    Epigenetic reprogramming is a hallmark of cancer. Here the authors find that resetting primed human embryonic stem cells to naïve state results in the acquisition of a DNA methylation landscape that mirrors the cancer DNA methylome and provides evidence that the transition to naïve pluripotency and oncogenic transformation share common epigenetic trajectories.

    • Hemalvi Patani
    • , Michael D. Rushton
    •  & Gabriella Ficz

  • Article
    | Open Access

    In mammals, DNA methylation patterns are established by two de novo DNA methyltransferases, DNMT3A and DNMT3B. Here the authors report the crystal structures of DNMT3B in complex with both CpG and CpA DNA, providing insight into the substrate-recognition mechanism underpinning the divergent genomic methylation activities of DNMT3A and DNMT3B.

    • Linfeng Gao
    • , Max Emperle
    •  & Jikui Song

  • Article
    | Open Access

    The molecular and physical mechanisms underlying chromatin folding at the single DNA molecule level remain poorly understood. Here, the authors use polymer modeling to investigate the conformations of two 2Mb-wide DNA loci in normal and cohesin depleted cells, and provide evidence that the architecture of the studied loci is controlled by a thermodynamics mechanism of polymer phase separation whereby chromatin self-assembles in segregated globules.

    • Mattia Conte
    • , Luca Fiorillo
    •  & Mario Nicodemi

  • Article
    | Open Access

    Epigenetic regulation can silence transposons and maintain gene expression. Here the authors survey Arabidopsis mutants defective in epigenetic regulation and show ectopic activation of thousands of cryptic TSSs and altered expression of nearby genes demonstrating the importance of suppressing spurious transcription.

    • Ngoc Tu Le
    • , Yoshiko Harukawa
    •  & Hidetoshi Saze

  • Article
    | Open Access

    Protein arginine deiminase 4 (PAD4) facilitates the posttranslational citrullination of histones H3 and H4. Here, the authors provide evidence that PAD4 antagonizes histone methylglyoxal-glycation by rewriting the glycated arginine into citrulline and protecting the reactive sites from further glycation.

    • Qingfei Zheng
    • , Adewola Osunsade
    •  & Yael David

  • Article
    | Open Access

    De novo DNA methylation is carried out by DNMT3A and DNMT3B, but the distinct functions of these two enzymes is poorly understood. Here the authors present a comprehensive, genome-wide identification of target sites for de novo DNA methylation by the DNMT3A and DNMT3B in mouse ES cells and embryos, identifying unique de novo DNA methylation target sites for both DNMT3 enzymes.

    • Masaki Yagi
    • , Mio Kabata
    •  & Yasuhiro Yamada

  • Article
    | Open Access

    MeCP2 is a transcriptional repressor and associates with nucleosomes. Here the authors show interaction of MeCP2 and H3K27me3 by biochemical assay and chromatin immunoprecipitation sequencing analysis.

    • Wooje Lee
    • , Jeeho Kim
    •  & Qizhi Gong

  • Article
    | Open Access

    CENP-A is a stable centromere mark, although active transcription poses a potential threat for retaining CENP-A through chromatin remodeling and nucleosome eviction. Here, the authors show that maintenance of the centromeric mark is preserved by Spt6, which recycles CENP-A nucleosomes.

    • Georg O. M. Bobkov
    • , Anming Huang
    •  & Patrick Heun

  • Article
    | Open Access

    Post-translational modifications of proteins at DNA damage sites can facilitate the recruitment of DNA repair factors. Here, the authors show that mRNA is locally modified with m5C at sites of DNA damage by the RNA methyltransferase TRDMT1 to promote homologous recombination repair.

    • Hao Chen
    • , Haibo Yang
    •  & Li Lan

  • Article
    | Open Access

    In S. pombe, small non-coding RNA mediates heterochromatin formation by recruiting the nucleosome remodeling and histone deacetylase complex. Here, the authors show that fly nucleosome remodeler Mi-2 and histone deacetylase Rpd3 are involved in piRNA-dependent transcriptional silencing of transposable elements.

    • Bruno Mugat
    • , Simon Nicot
    •  & Séverine Chambeyron

  • Article
    | Open Access

    Mediator is a multiprotein complex required to activate gene transcription by RNAPII. Here, the authors report that MED12 and MED13 are conditional positive regulators that facilitate the expression of genes depleted in active chromatin marks and the induction of gene expression in response to environmental stimuli in Arabidopsis.

    • Qikun Liu
    • , Sylvain Bischof
    •  & Steven E. Jacobsen

  • Article
    | Open Access

    Obesity and type 2 diabetes (T2D) are metabolic disorders characterized by insulin resistance in skeletal muscle. Here, the authors map skeletal muscle enhancer elements dynamically regulated after exposure to free fatty acid palmitate or inflammatory cytokine TNFα and identify target genes involved in metabolic dysfunction in skeletal muscle.

    • Kristine Williams
    • , Lars R. Ingerslev
    •  & Romain Barrès

  • Article
    | Open Access

    Local activity of the DNA methylation machinery remains poorly understood. Here, the authors present a theoretical and experimental framework to infer methylation and demethylation rates at genome scale in mouse embryonic stem cells, finding that maintenance methylation activity is reduced at transcription factor binding sites, while methylation turnover is elevated in transcribed gene bodies.

    • Paul Adrian Ginno
    • , Dimos Gaidatzis
    •  & Dirk Schübeler

  • Article
    | Open Access

    DNA methylation is an epigenetic marker in all domains of life. Here, Jeudy et al., using single-molecule realtime sequencing, determine DNA methylation patterns in giant viruses and evolutionary analysis of virus encoded DNA methyltransferases suggests that they affect viral fitness.

    • Sandra Jeudy
    • , Sofia Rigou
    •  & Matthieu Legendre

  • Article
    | Open Access

    While DNA methylation is thought to play a regulatory role, there are few examples where modification of a single CpG dinucleotide directly affects transcription factor binding. Here the authors show that methylation of a single CGATA element within the c-Kit gene inhibits binding and regulation by erythroid transcription factor GATA-1, both in cells and in mice, suggesting that methylation at this site plays an essential role in erythropoiesis.

    • Lu Yang
    • , Zhiliang Chen
    •  & Merlin Crossley

  • Article
    | Open Access

    TRANSPARENT TESTA19 (TT19) encodes a glutathione S-transferase which functions in anthocyanin stabilization and vacuolar transport. Here, by tt19 suppressor screening, the authors show that RDR6/SGS3/DCL4 siRNA pathway constituents synergistically interact with components of the flavonoid pathway to control carbon metabolism.

    • Nan Jiang
    • , Aimer Gutierrez-Diaz
    •  & Erich Grotewold

  • Article
    | Open Access

    In fission yeast, several lncRNAs act in cis to regulate expression of adjacent genes. Here, the authors show that the conserved Pir2ARS2 protein is targeted, along with splicing factors, to cryptic introns in lncRNAs and recruits effectors, including RNAi machinery, for gene repression.

    • Gobi Thillainadesan
    • , Hua Xiao
    •  & Shiv I. S. Grewal

  • Article
    | Open Access

    Early life exposure to environmental stressors, including endocrine disrupting chemicals (EDCs), can impact health later in life. Here, the authors show that neonatal EDC exposure in rats causes epigenetic reprogramming in the liver, which is transcriptionally silent until animals are placed on a Western-style diet.

    • Lindsey S. Treviño
    • , Jianrong Dong
    •  & Cheryl Lyn Walker

  • Article
    | Open Access

    The DNA methyltransferase DNMT3A plays an important role in establishing the DNA methylation patterns during development and deregulation of DNMT3A is associated with hematological cancers, with the R882H mutation the most frequently occurring DNMT3A missense mutation in acute myeloid leukemia. Here, the authors present the crystal structures of wild-type and R882H DNMT3A in complex with different DNA substrates and explain why the R882H mutation compromises the enzymatic activity of DNMT3A.

    • Hiwot Anteneh
    • , Jian Fang
    •  & Jikui Song

  • Article
    | Open Access

    The MOF acetyltransferase-containing Non-Specific Lethal (NSL) complex is a broad transcription regulator and haploinsufficiency of its KANSL1 subunit results in the Koolen-de Vries syndrome in humans. Here, the authors identify the BET protein BRD4 as evolutionary conserved co-factor of the NSL complex and provide evidence that NSL-deposited histone acetylation induces BRD4 recruitment for transcription of constitutively active genes.

    • Aline Gaub
    • , Bilal N. Sheikh
    •  & Asifa Akhtar

  • Article
    | Open Access

    ATRX is an RNA binding protein that mediates targeting of polycomb repressive complex 2 (PRC2) to genomic sites. Here the authors identify the RNA binding region and show that the RNA binding is required for ATRX localization and for its recruitment of PRC2 to a subset of polycomb targets.

    • Wenqing Ren
    • , Nicole Medeiros
    •  & Kavitha Sarma

  • Article
    | Open Access

    Segregation of an MSH1 RNAi transgene produces non-genetic memory that displays transgenerational inheritance in Arabidopsis. Here, the authors compare memory and non-memory full-sib progenies to show the involvement of DNA methylation reprogramming, involving the RdDM pathway, in transition to a heritable memory state.

    • Xiaodong Yang
    • , Robersy Sanchez
    •  & Sally A. Mackenzie

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