DNA methylation articles within Nature Communications

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  • Article
    | Open Access

    Whether thyroid hormones affect gene expression via DNA methylation is not well known. Here the authors show that type 2 deiodinase (D2) converts T4 to produce T3, which prevents DNA methylation of discrete areas in the neonatal liver. In the absence of D2, DNA methylation occurs and is associated with reduced chromatin accessibility in promoters and enhancers and affects gene expression.

    • Tatiana L. Fonseca
    • , Tzintzuni Garcia
    •  & Antonio C. Bianco

  • Article
    | Open Access

    MORC ATPases are required for transposable element silencing and heterochromatin condensation in plants and animals. Here the authors show that Arabidopsis MORCs colocalize with sites of RNA-directed DNA methylation and provide evidence that they act as molecular tethers to efficiently establish DNA methylation.

    • Yan Xue
    • , Zhenhui Zhong
    •  & Steven E. Jacobsen

  • Article
    | Open Access

    Charting the landscape of 5hmC in human tissues is fundamental to understanding its regulatory functions. Here, we systematically profiled the whole-genome 5hmC landscape at single-base resolution for 19 types of human tissues and found 5hmC shows tissue-specific patterns.

    • Bo He
    • , Chao Zhang
    •  & Chengqi Yi

  • Article
    | Open Access

    α-ketoglutarate (αKG) is an intermediate in the tricarboxylic acid cycle that is required in the nucleus for genomic DNA demethylation by Tet3. Here, the authors show that the enzyme glutamate dehydrogenase, which converts glutamate to αKG, is redirected from the mitochondria to the nucleus.

    • Franziska R. Traube
    • , Dilara Özdemir
    •  & Thomas Carell

  • Article
    | Open Access

    In most mammals, imprinted genes contain epigenetic marks that differ in each parental genome and control their parent-of-origin-specific expression. Here, the authors map imprinted genes in mouse preimplantation embryos and find that imprinted gene expression in blastocysts is mainly dependent on Polycomb-mediated H3K27me3-associated gene silencing.

    • Laura Santini
    • , Florian Halbritter
    •  & Martin Leeb

  • Article
    | Open Access

    DNA methylation targets CpG island promoters of germline genes to repress their expression in mouse somatic cells. Here the authors show that a transcription factor E2F6 is required to target CpG island DNA methylation and epigenetic silencing to germline genes during early mouse development.

    • Thomas Dahlet
    • , Matthias Truss
    •  & Michael Weber

  • Article
    | Open Access

    The functional relevance of epigenetic modifications on transcription regulation has been an important question since their discovery. Here, the authors investigate the effect of DNA methylation on Pioneer Transcription Factor (PF) binding and distinguish between PFs that protect their binding sites from methylation and those that bind to methylated DNA and induce DNA demethylation.

    • Ludovica Vanzan
    • , Hadrien Soldati
    •  & Rabih Murr

  • Article
    | Open Access

    Myelin formation is regulated by epigenetic mechanisms and ensures proper neuronal function during development and after demyelination. Here, the authors show that TET1, a DNA hydroxymethylase, regulates myelin repair in adult mice, but is defective with aging.

    • Sarah Moyon
    • , Rebecca Frawley
    •  & Patrizia Casaccia

  • Article
    | Open Access

    In plants, RNA-directed DNA methylation (RdDM) is a de novo DNA methylation pathway that is responsible for transcriptional silencing of repetitive elements. Here, the authors characterized a new RdDM factor, RDM15, and show that it is required for RdDM-dependent DNA methylation and siRNA accumulation at a subset of RdDM target loci.

    • Qingfeng Niu
    • , Zhe Song
    •  & Zhaobo Lang

  • Article
    | Open Access

    Multi-layered epigenetic regulation in higher eukaryotes makes it challenging to disentangle the individual effects of modifications on chromatin structure and function. Here, the authors expressed mammalian DNA methyltransferases in yeast, which have no DNA methylation, to show that methylation has intrinsic effects on chromatin structure.

    • Diana Buitrago
    • , Mireia Labrador
    •  & Modesto Orozco

  • Article
    | Open Access

    The ability to target DNA methylation to specific loci is important for both basic and applied research. Here, the authors fuse CG-specific methyltransferase SssI with an artificial zinc finger protein for DNA methylation targeting and show the chromatin features favorable for efficient gain of methylation.

    • Wanlu Liu
    • , Javier Gallego-Bartolomé
    •  & Steven E. Jacobsen

  • Article
    | Open Access

    While coffee and tea consumption has been associated with risk of diseases, their mechanisms of action remain elusive. Here the authors present a large EWAS on coffee and tea consumption in cohorts of European and African-American ancestries, finding that coffee consumption is associated with differential DNA methylation levels at multiple CpGs.

    • Irma Karabegović
    • , Eliana Portilla-Fernandez
    •  & Mohsen Ghanbari

  • Article
    | Open Access

    Accumulating evidences point to a discrepancy in the epigenetic behaviour of transgenes and endogenous genes. Here, via characterization of mutants impaired in histone demethylases JMJ14 and IBM1, the authors show that transgenes and endogenous genes are regulated by different epigenetic mechanisms in Arabidopsis.

    • Nicolas Butel
    • , Agnès Yu
    •  & Hervé Vaucheret

  • Article
    | Open Access

    T-DNA mutants have been widely used for Arabidopsis gene function characterization. Here, by characterizing a null mutant created by CRISPR, the authors show that previous reported function of H2A.W is confounded by a T-DNA insertion induced chromosomal rearrangement and reveal its role in regulating heterochromatin accessibility.

    • Pierre Bourguet
    • , Colette L. Picard
    •  & Olivier Mathieu

  • Article
    | Open Access

    Tissue damage and turnover lead to the release of DNA in the blood and can be used to monitor changes in tissue state. Here, the authors developed a tool to accurately estimate the proportion of cell types contributing to cell-free DNA in the blood, with an application to pregnant women and ALS patients.

    • Christa Caggiano
    • , Barbara Celona
    •  & Noah Zaitlen

  • Article
    | Open Access

    How histone modifications crosstalk with DNA methylation to regulate epigenomic patterning and genome stability in mammals remains elusive. Here, the authors show that DNA methyltransferase DNMT1 is a reader for histone H4K20 trimethylation via its BAH1 domain, which leads to optimal maintenance of DNA methylation at repetitive LINE-1 elements.

    • Wendan Ren
    • , Huitao Fan
    •  & Jikui Song

  • Article
    | Open Access

    Insulin resistance and lower muscle strength in relation to mass are hallmarks of type 2 diabetes. Here, the authors report alterations in muscle stem cells from individuals with type 2 diabetes that may contribute to these phenotypes through VPS39 mediated effects on autophagy and epigenetics.

    • Cajsa Davegårdh
    • , Johanna Säll
    •  & Charlotte Ling

  • Article
    | Open Access

    B cell progenitors differentiate into multiple subsets with distinct functions. Here the authors analyze the epigenetic landscapes of sorted B cell subsets using multiple platforms and show that the epigenetic regulator, DNMT3A, is essential for modulating the activity of enhancers critical for B1 and B2 lineage-determining genes.

    • Vinay S. Mahajan
    • , Hamid Mattoo
    •  & Shiv Pillai

  • Article
    | Open Access

    DNA methylation turnover is an essential epigenetic process during development. Here, the authors look at the changes in DNA methylation during the differentiation of post-mitotic human monocytes (MO), and find that EGR2 interacts with TET2 and is required for DNA demethylation at its binding sites; revealing EGR2 as an epigenetic pioneer factor in human MO.

    • Karina Mendes
    • , Sandra Schmidhofer
    •  & Michael Rehli

  • Article
    | Open Access

    Erasure of DNA methylation from the parental genomes is critical to reset the methylome of differentiated gametes to pluripotent cells in the blastocyst. Here, the authors present a high-throughput single-cell method that enables strand-specific quantification of DNA methylation and identify distinct modes of DNA demethylation dynamics during early mammalian development.

    • Maya Sen
    • , Dylan Mooijman
    •  & Alexander van Oudenaarden

  • Article
    | Open Access

    Extensive epigenetic reprogramming occurs during preimplantation embryo development. Here the authors develop a single cell multiomics sequencing technology that enables profiling of genome-wide chromatin accessibility, DNA methylation and RNA expression in the same individual cell and apply this method to study mouse preimplantation embryos.

    • Yang Wang
    • , Peng Yuan
    •  & Liying Yan

  • Article
    | Open Access

    Aberrant gain of DNA methylation at CpG islands is frequently observed in colorectal tumours. Here the authors use ectopically integrated CpG islands in colorectal cancer cells and find that aberrantly methylated CpG islands are subject to low levels of de novo DNA methylation, and that instead de novo DNA methylation activity is targeted primarily to CpG islands marked by the histone modification H3K36me3.

    • Roza H. Ali Masalmeh
    • , Francesca Taglini
    •  & Duncan Sproul

  • Article
    | Open Access

    Mesenchymal stromal cells (MSCs) have been shown to support multiple myeloma (MM) development. Here, MSCs isolated from the bone marrow of MM patients are shown to have altered DNA methylation patterns and a methyltransferase inhibitor reverts MM-associated bone loss and reduces tumour burden in MM murine models.

    • Antonio Garcia-Gomez
    • , Tianlu Li
    •  & Esteban Ballestar

  • Article
    | Open Access

    Here, the authors introduce Cell Heterogeneity–Adjusted cLonal Methylation (CHALM) as a methylation quantification method that considers the heterogeneity of sequenced bulk cells. They apply CHALM to methylation datasets to detect differentially methylated genes that exhibit distinct biological functions supporting underlying mechanisms.

    • Jianfeng Xu
    • , Jiejun Shi
    •  & Wei Li

  • Article
    | Open Access

    Acidothermus cellulolyticus CRISPR-Cas9 (AceCas9) is a Type II-C enzyme that cleaves DNA in a Protospacer Adjacent Motif (PAM) methylation sensitive fashion. Biochemical analysis and crystal structures of AceCas9 in complex with sgRNA and DNA bearing the correct and incorrect PAM offer insight into the structural basis for the recognition of PAM and its methylation.

    • Anuska Das
    • , Travis H. Hand
    •  & Hong Li

  • Article
    | Open Access

    DNA 5-hydroxymethylcytosine (5hmC) modification is associated with gene transcription and used as a mark of mammalian development. Here the authors report a comprehensive 5hmC tissue map and analysis of 5hmC genomic distributions in 19 human tissues derived from 10 organ systems, thus providing insights into the role of 5hmC in tissue-specific development.

    • Xiao-Long Cui
    • , Ji Nie
    •  & Chuan He

  • 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

    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

    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

    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

    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

    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

    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

    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

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