Epigenetics articles within Nature Communications

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  • Article
    | Open Access

    The treatment of brain metastases is often limited by the ability to diagnose their origins. Here the authors generate DNA methylomes from the three most frequent types of brain metastases, identify epigenetic signatures specific to each type of metastasis and construct a DNA methylation-based classifier (BrainMETH) to advance brain metastasis diagnosis.

    • Javier I. J. Orozco
    • , Theo A. Knijnenburg
    •  & Diego M. Marzese

  • Article
    | Open Access

    DNA methylation and H3K9 dimethylation are two linked epigenetic marks of silenced chromatin in plants that depend on the activity of CMT3/2 and SUVH4/5/6. Here the authors identify AGDP1 as an H3K9me2-binding protein required for heterochromatic non-CG DNA methylation, H3K9 dimethylation, and transcriptional silencing.

    • Cuijun Zhang
    • , Xuan Du
    •  & Jian-Kang Zhu

  • Article
    | Open Access

    Primordial Germ Cell-Like Cells (PGCLCs) are an in vitro model for primordial germ cell development. Here, the authors couple a novel compound reporter with CRISPR screening to identify key genes for exit from pluripotency and acquisition of PGCLC fate; specifically identifying Nr5a2 and Zfp296.

    • Jamie A. Hackett
    • , Yun Huang
    •  & M. Azim Surani

  • Article
    | Open Access

    PWWP2A is a chromatin-binding transcriptional regulator that mediates mitosis-progression. Here, the authors provide evidence that PWWP2A directly interacts with H2A.Z nucleosomes, DNA and H3K36me3, binds to an MTA1-specific subcomplex of the NuRD complex (M1HR) and promotes changes to histone acetylation.

    • Stephanie Link
    • , Ramona M. M. Spitzer
    •  & Sandra B. Hake

  • Article
    | Open Access

    miR-34 is known to regulate age-related gene expression in the Drosophila brain, and miR-34 overexpression can attenuate neurodegeneration induced by polyQ-expanded proteins. Here, Kennerdell and colleagues show that miR-34 confers longevity and neuroprotection via an epigenetic regulator Polycomb Repressive Complex 2 and molecular chaperone expression.

    • Jason R. Kennerdell
    • , Nan Liu
    •  & Nancy M. Bonini

  • Article
    | Open Access

    The role of the genome structure in the establishment of the embryonic and trophoblast lineages is still not well understood. Here the authors perform promoter capture Hi-C in mouse trophoblast and embryonic stem cells and find divergent networks of repressive and active chromatin interactions between the two lineages.

    • Stefan Schoenfelder
    • , Borbala Mifsud
    •  & Miguel R. Branco

  • Article
    | Open Access

    Epigenetic regulation is critical for the maintenance of germ cell identity. Here the authors show that H3K9me3-mediated gene silencing is critical for repression of testis-specific transcription in Drosophila female germ cells, indicating H3K9me3 maintains female germ cell sexual identity.

    • Anne E. Smolko
    • , Laura Shapiro-Kulnane
    •  & Helen K. Salz

  • Article
    | Open Access

    Mitosis poses a challenge for transcriptional programs, as it is thought that several proteins lose binding on condensed chromosomes. Here, the authors analyze the chromatin-bound proteome through the cell cycle, revealing retention of most transcription factors and preservation of the regulatory landscape.

    • Paul Adrian Ginno
    • , Lukas Burger
    •  & Dirk Schübeler

  • Article
    | Open Access

    Around 10% of high-grade serous ovarian carcinomas (HGSOC) harbor BRCA1 promoter methylation, but it is uncertain how it predicts response to PARP inhibition. Here, the authors show that homozygous BRCA1 methylation predicts response to rucaparib while heterozygous methylation of BRCA1 predicts resistance in HGSOC.

    • Olga Kondrashova
    • , Monique Topp
    •  & Clare L. Scott

  • Article
    | Open Access

    The Polycomb Repressive-Deubiquitinase (PR-DUB) complex is responsible for the removal of the ubiquitin epigenetic modification from Histone 2A. Here the authors describe the structure of the Drosophila PR-DUB complex, providing new insight into its regulation and how cancer-associated mutations disrupt PR-DUB activity.

    • Martina Foglizzo
    • , Adam J. Middleton
    •  & Peter D. Mace

  • Article
    | Open Access

    Loss of Polycomb repressive complex 1 (PRC1) proteins usually results in both chromatin unfolding and ectopic transcription. Here, the authors analyze the temporal function of two PRC1 proteins during Drosophila embryogenesis and provide evidence that PRC1 maintains gene silencing by folding chromatin domains.

    • Thierry Cheutin
    •  & Giacomo Cavalli

  • Article
    | Open Access

    While a majority of histones are replaced by protamines during spermatogenesis, a small amount is retained in mammalian spermatozoa. Here the authors develop a method to purify histones from replacement-completed sperm (HRCS), completely solubilize histones from cross-linked HRCS without MNase digestion, and map histone-binding sites in these cells.

    • Keisuke Yoshida
    • , Masafumi Muratani
    •  & Shunsuke Ishii

  • Article
    | Open Access

    Single-cell DNA methylome profiling allows the study of epigenomic heterogeneity in tissues but has been impeded by library quality. Here the authors demonstrate snmC-seq2 which improves mapping, throughput and library complexity.

    • Chongyuan Luo
    • , Angeline Rivkin
    •  & Joseph R. Ecker

  • Article
    | Open Access

    Although Ftx lncRNA has been linked to X-chromosome inactivation, its physiological roles in vivo remain unclear. Here the authors show that deletion of mouse Ftx causes eye abnormalities similar to human microphthalmia in a subset of female mice but rarely in males and provide evidence that Ftx plays a role in gene silencing on the inactive X chromosome.

    • Yusuke Hosoi
    • , Miki Soma
    •  & Shin Kobayashi

  • Article
    | Open Access

    In Drosophila the Male-Specific Lethal complex (MSLc) mediates upregulation of the single male X chromosome. Here the authors provide evidence that MSL2 also targets autosomal genes required for proper development and that MSL2 binds and similarly regulates mouse orthologues.

    • Claudia Isabelle Keller Valsecchi
    • , M. Felicia Basilicata
    •  & Asifa Akhtar

  • Article
    | Open Access

    The Mll3/4 histone methyltransferases can act as tumour suppressors in humans. Here, the authors identify three orthologs of mammalian MLL3/4 in the planarian Schmidtea mediterranea and show that knockdown causes outgrowths in regenerating animals, suggesting that the tumour suppressive function of these genes is deeply conserved.

    • Yuliana Mihaylova
    • , Prasad Abnave
    •  & A. Aziz Aboobaker

  • Article
    | Open Access

    Brown adipose tissue (BAT) thermogenesis counteracts obesity and promotes metabolic health. The role of long non-coding RNAs (lncRNAs) in the regulation of this process is not well understood. Here the authors identify a maternally expressed lncRNA, H19, that increases BAT oxidative metabolism and energy expenditure.

    • Elena Schmidt
    • , Ines Dhaouadi
    •  & Jan-Wilhelm Kornfeld

  • Article
    | Open Access

    The expression of CD4, a critical co-receptor providing T cell help in adaptive immunity, is finely tuned during development. Here the authors show that two enhancer elements, E4p and the newly-defined E4m, coordinate the expression and heritable demethylation of Cd4 in thymocytes but are dispensable for its sustained expression in peripheral T cells.

    • Priya D. Issuree
    • , Kenneth Day
    •  & Dan R. Littman

  • Article
    | Open Access

    Suppression of gene expression due to aberrant promoter methylation contributes to organ fibrosis. Here, the authors couple a deactivated Cas9 to the TET3 catalytic domain to induce expression of four antifibrotic genes, and show that lentiviral-mediated delivery is effective in reducing kidney fibrosis in mouse models.

    • Xingbo Xu
    • , Xiaoying Tan
    •  & Michael Zeisberg

  • Comment
    | Open Access

    Over the past decade, remarkable breakthroughs in our understanding of epigenetic biology have coincided with an increased public interest in the impact of diet and lifestyle choices on health. It is well established that a balanced diet enhances life expectancy and helps to prevent or treat certain diseases, such as obesity, diabetes, cancer, and mental disorders. However, the biological mechanisms underlying these effects are not yet well understood. In this commentary, we highlight several recent studies that report on a potential link between dietary factors and alterations in epigenetic pathways, providing compelling insight into the possible effects of environmental factors on fundamental biological processes.

    • Yi Zhang
    •  & Tatiana G. Kutateladze

  • Article
    | Open Access

    Histone marks regulate chromatin structure and function. Here the authors identify and characterize lysine benzoylation, a histone mark that can be modulated by sodium benzoate, a widely used chemical food preservative, associated with specific regulation of gene expression.

    • He Huang
    • , Di Zhang
    •  & Yingming Zhao

  • Article
    | Open Access

    Development may be plastic and influenced by parental care. Here, the authors show that experimental reduction of maternal care in the small carpenter bee leads to extensive changes in gene expression and splicing, minor changes in methylation, and greater offspring aggression and social avoidance.

    • Samuel V. Arsenault
    • , Brendan G. Hunt
    •  & Sandra M. Rehan

  • Article
    | Open Access

    The role of Polycomb Repressive Complex 1 (PRC1) is well described in development. Here, the authors investigate canonical PRC1’s regulation of transcriptional programs in breast cancer where, in addition to its repressive function, it is also recruited to oncogenic active enhancers to regulate enhancer activity and chromatin accessibility.

    • Ho Lam Chan
    • , Felipe Beckedorff
    •  & Lluis Morey

  • Article
    | Open Access

    De novo DNA methylation during mouse oogenesis occurs within transcribed regions. Here the authors investigate the role of species-specific long terminal repeats (LTRs)-initiated transcription units in regulating the oocyte methylome, identifying syntenic regions in mouse, rat and human with divergent DNA methylation associated with private LITs.

    • Julie Brind’Amour
    • , Hisato Kobayashi
    •  & Matthew C. Lorincz

  • Article
    | Open Access

    Immunoglobulin E (IgE)-mediated food allergy is a major issue that affects 2–10% of infants. Here the authors study the epigenetic regulation of the naive CD4+ T cell activation response among children with IgE-mediated food allergy finding epigenetic dysregulation in the early stages of signal transduction through the T cell receptor complex.

    • David Martino
    • , Melanie Neeland
    •  & Richard Saffery

  • Article
    | Open Access

    Epigenetic modifications are a key contributor to cell identity, and their propagation is crucial for proper development. Here the authors use a super-resolution microscopy approach to reveal how histone variants are faithfully transmitted during genome duplication, and reveal an important role for the histone chaperone ASF1 in the redistribution of parental histones.

    • Camille Clément
    • , Guillermo A. Orsi
    •  & Geneviève Almouzni

  • Article
    | Open Access

    Myelin-forming cells derive from oligodendrocyte progenitors. Here the authors identify histone arginine methyl-transferase PRMT5 as critical for developmental myelination by modulating the cross-talk between histone arginine methylation and lysine acetylation, to favor differentiation.

    • Antonella Scaglione
    • , Julia Patzig
    •  & Patrizia Casaccia

  • Article
    | Open Access

    Genomic imprinting restricts transcription to predominantly one parental allele. Here the authors perform a screen for epigenetic factors involved in paternal allelic silencing at the Kcnq1ot1 imprinted domain in mouse extraembryonic endoderm stem cells and characterize a role for specific nucleoporins in mediating Kcnq1ot1 imprinted regulation.

    • Saqib S. Sachani
    • , Lauren S. Landschoot
    •  & Mellissa R. W. Mann

  • Article
    | Open Access

    ASXL1 gene is often mutated in myeloid malignancies. Here, the authors show that mutant ASXL1 and BAP1 are in a positive feedback loop such that BAP1 induces monoubiquitination of mutant ASXL1, which in turn enhances BAP1 activity to potentiate myeloid transformation via HOXA clusters and IRF8.

    • Shuhei Asada
    • , Susumu Goyama
    •  & Toshio Kitamura

  • Article
    | Open Access

    Uhrf1 is a known regulator of heterochromatin and DNA methylation in embryonic stem cells (ESCs). Here, the authors demonstrate that Uhrf1 acts together with the Set1/COMPASS complex regulator of active transcription to promote H3K4 methylation at bivalent loci and Uhrf1 loss results in disruption of differentiation.

    • Kun-Yong Kim
    • , Yoshiaki Tanaka
    •  & In-Hyun Park

  • Article
    | Open Access

    Sex differences in placental O-linked N-acetylglucosamine transferase (OGT) activity mediate the effects of prenatal stress on neurodevelopmental programming. Here authors provide evidence that OGT confers variation in vulnerability to prenatal insults by establishing sex-specific trophoblast gene expression via regulation of H3K27me3.

    • Bridget M. Nugent
    • , Carly M. O’Donnell
    •  & Tracy L. Bale

  • Article
    | Open Access

    Histone mark reader proteins bind to particular histone modifications and regulate chromatin state. Here, Qian et al. show that the SHORT LIFE reader has a unique ability to recognize both activating and repressive histone marks and that these interactions enable SHORT LIFE to repress flowering in plants.

    • Shuiming Qian
    • , Xinchen Lv
    •  & Jiamu Du

  • Article
    | Open Access

    Single cell ATAC-seq (scATAC-seq) data reveals cellular level epigenetic heterogeneity but its application in delineating distinct subpopulations is still challenging. Here, the authors develop scABC, a statistical method for unsupervised clustering of scATAC-seq data and identification of open chromatin regions specific to cell identity.

    • Mahdi Zamanighomi
    • , Zhixiang Lin
    •  & Wing Hung Wong

  • Article
    | Open Access

    To comprehend the genetic regulatory mechanisms underlying brain-related traits in humans, Qi et al. estimate the correlation of expression and DNA methylation QTL effects in cis between blood and brain and show that using blood eQTL/mQTL data of large sample size  can increase power in gene discovery for brain-related traits and diseases.

    • Ting Qi
    • , Yang Wu
    •  & Jian Yang

  • Article
    | Open Access

    Steatosis is characterized by initial accumulation of lipids, followed by inflammation and ultimately fibrosis. Here the authors show that the histone demethylase Plant Homeodomain Finger 2 protects liver form steatosis progression by acting as a co-activator of ChREBP, thus, favouring lipid accumulation without inflammation.

    • Julien Bricambert
    • , Marie-Clotilde Alves-Guerra
    •  & Renaud Dentin

  • Article
    | Open Access

    A proportion of neurodevelopmental disorder and congenital anomaly cases remain without a genetic diagnosis. Here, the authors study aberrations of DNA methylation in such cases and find that epivariations might provide an explanation for some of these undiagnosed patients.

    • Mafalda Barbosa
    • , Ricky S. Joshi
    •  & Andrew J. Sharp

  • Article
    | Open Access

    Here the authors show that a large fraction of the tissue-specific methylation pattern is generated postnatally. These changes, which occur in response to hormone signaling, appear to play a major role in the regulation of gene expression and tissue maturation in the liver.

    • Yitzhak Reizel
    • , Ofra Sabag
    •  & Howard Cedar

  • Article
    | Open Access

    Adoptive T cell therapy using an allogeneic T cell graft is an encouraging therapeutic approach in cancer, but issues such as graft-versus-host disease can hinder applicability. Here, the authors show that DOT1L inhibition or DUSP6 overexpression in T cells attenuates graft-versus-host disease but retains anti-tumour activity in mouse models.

    • Yuki Kagoya
    • , Munehide Nakatsugawa
    •  & Naoto Hirano

  • Article
    | Open Access

    Polycomb-group proteins are key regulators of transcriptional programs that maintain cell identity. Here the authors provide evidence that PCGF5, a subunit of Polycomb Repressor Complex 1, is important for the differentiation of mouse embryonic stem cells towards a neural cell fate.

    • Mingze Yao
    • , Xueke Zhou
    •  & Hongjie Yao

  • Article
    | Open Access

    In mammalian female germ cells, parent-specific epigenetic marks are erased and the X chromosome reactivated before entry into meiosis. Here, by combining parental haplotype reconstruction with single-cell transcriptomics of human female embryonic germ cells, the authors demonstrate that epigenetic reprogramming occurs in a heterogeneous fashion and during a broad time window up to week 14.

    • Ábel Vértesy
    • , Wibowo Arindrarto
    •  & Susana M. Chuva de Sousa Lopes

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