Epigenetics articles within Nature Communications

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  • Article
    | Open Access

    Age is a risk factor for SARS-CoV-2 infection and severe disease. Here the authors perform DNA methylation analyses in whole blood from COVID-19 patients using established epigenetic clocks and telomere length estimators, and describing correlations between epigenetic aging and the risk of SARS-CoV-2 infection and severe disease.

    • Xue Cao
    • , Wenjuan Li
    •  & Huichuan Yu

  • Article
    | Open Access

    The genus Quercus (oaks) has diversified into over 450 species which often play dominant roles in the ecosystems in which they occur. Here the authors present a genome and methylome for a California endemic oak, Quercus lobata, and describe features relevant to its evolutionary success.

    • Victoria L. Sork
    • , Shawn J. Cokus
    •  & Steven L. Salzberg

  • Article
    | Open Access

    Timing of assisted reproduction technology (ART) procedures coincides with extensive epigenetic remodeling early after conception. Here the authors identify 176 DNA methylation differences in cord blood of newborns conceived with ART. including genes related to growth, neurodevelopment, and cancer.

    • Siri E. Håberg
    • , Christian M. Page
    •  & Robert Lyle

  • Article
    | Open Access

    The concerted dynamics of X-chromosome upregulation and X-chromosome inactivation, which collectively balance X-chromosome expression, are not well understood. Using allelic single-cell genomics, the authors characterize the dynamics of X-chromosome upregulation and inactivation along mouse embryonic and stem cell development, calling to question keys aspects of the established model of mammalian dosage compensation.

    • Antonio Lentini
    • , Huaitao Cheng
    •  & Björn Reinius

  • Article
    | Open Access

    The ability to predict epigenetic regulation is an important challenge in biology. Here the authors describe heterochromatin nanodomains (HNDs) and compare four different types of H3K9me2/3-marked HNDs in mouse embryonic stem cells. They further develop a computational framework to predict genome-wide HND maps from DNA sequence and protein concentrations, at single-nucleotide resolution.

    • Graeme J. Thorn
    • , Christopher T. Clarkson
    •  & Vladimir B. Teif

  • Article
    | Open Access

    Female embryonic stem cells (ESCs) are the ideal model to study X chromosome inactivation (XCI) establishment; however, these cells are challenging to keep in culture. Here the authors create fluorescent ‘Xmas’ reporter mice as a renewable source of ESCs and show nucleosome remodelers Smarcc1 and Smarca4 create a nucleosome-free promoter region prior to the establishment of silencing.

    • Andrew Keniry
    • , Natasha Jansz
    •  & Marnie E. Blewitt

  • Article
    | Open Access

    Epigenetic states that are established during thymic T cell development influence functionality of mature T cells. Authors here show that early developmental programming of the Cd4 locus is comprised of DNA-demethylation at a specific stimulus-responsive element, which allows long-term maintenance of activator histone H3K4 trimethylation and transcription.

    • Athmane Teghanemt
    • , Priyanjali Pulipati
    •  & Priya D. Issuree

  • Article
    | Open Access

    Our understanding of the extent of involvement of DNA methylation in genome-wide gene regulation and plant developmental control is incomplete. Here, the authors knock out all five known DNA methyltransferases and show the developmental and gene expression changes in the DNA methylation-free Arabidopsis plants.

    • Li He
    • , Huan Huang
    •  & Jian-Kang Zhu

  • Article
    | Open Access

    Eukaryotic DNA can be methylated as 5-methylcytosine and N6-methyladenine, but whether other forms of DNA methylation occur has been controversial. Here the authors show that a bacterial DNA methyltransferase was acquired >60 Mya in bdelloid rotifers that catalyzes N4-methylcytosine addition and is involved in suppression of transposon proliferation.

    • Fernando Rodriguez
    • , Irina A. Yushenova
    •  & Irina R. Arkhipova

  • Article
    | Open Access

    Methods to probe DNA methylation in the majority of non-human mammals are lacking. Here the authors developed a Mammalian Methylation Array that includes 36k well-conserved CpGs in mammals which will facilitate cross-species comparisons. They annotate the conserved CpGs in > 200 species. The array allows one to measure methylation in all mammalian species including unsequenced ones.

    • Adriana Arneson
    • , Amin Haghani
    •  & Steve Horvath

  • Article
    | Open Access

    Transgenerational inheritance (TEI) mechanisms are to some extent conserved across species, but how TEI mediates lipid accumulation is unknown. Here the authors reveal that a network of lipid metabolic genes and chromatin modifications mediated by transcription factors and H3K4 trimethylation work together to achieve multigenerational obesogenic effects in C. elegans fed with a high-fat diet.

    • Qin-Li Wan
    • , Xiao Meng
    •  & Qinghua Zhou

  • Article
    | Open Access

    The link between 3D genome architecture and gene expression is still far from resolved. Here the authors show that loss of the CDK catalytic subunit of the Mediator complex results in heterochromatic silencing, which can be rescued by stabilization of cohesin on chromatin.

    • Judith H. I. Haarhuis
    • , Robin H. van der Weide
    •  & Elzo de Wit

  • Article
    | Open Access

    N6-methyladenosine (m6A) plays important role in lineage specifications of embryonic stem cells, but its role at specific sites has not been assessed. Here the authors develop an adenine editor-based strategy, and systematically identify functional m6A sites that control lineage decisions in human embryonic stem cells.

    • Weisheng Cheng
    • , Fang Liu
    •  & Jinkai Wang

  • Article
    | Open Access

    The transcription factor network required for primordial germ cell (PGC) specification is known to diverge in mammals. Here the authors show that hominidae-specific transposable element (TE) LTR5Hs becomes transcriptionally active during PGC specification, and LTR5Hs inactivation abrogates human PGC specification

    • Xinyu Xiang
    • , Yu Tao
    •  & Amander T. Clark

  • Article
    | Open Access

    The exceptionally long-lived naked mole-rat is characterized by the lack of increased mortality with aging. Here the authors perform epigenetic studies to show that naked mole-rats epigenetically age despite their non-increasing mortality rate.

    • Csaba Kerepesi
    • , Margarita V. Meer
    •  & Vadim N. Gladyshev

  • Article
    | Open Access

    Function of nucleosomal acetyltransferase of H4 (NuA4), one major complex of HAT, remains unclear in plants. Here, the authors generate mutants targeting two components of the putative NuA4 complex in Arabidopsis (EAF1 and EPL1) and show their roles in photosynthesis genes regulation through H4K5ac and H2A.Z acetylation.

    • Tomasz Bieluszewski
    • , Weronika Sura
    •  & Piotr A. Ziolkowski

  • Article
    | Open Access

    CLASSY (CLSY) proteins regulate DNA methylation at specific loci in the Arabidopsis genome. Here the authors show that the CLSYs also control tissue-specific DNA methylation, including at siren loci in ovules, and that the lack of an individual CLSYs can shift the epigenetic landscape between tissues.

    • Ming Zhou
    • , Ceyda Coruh
    •  & Julie A. Law

  • Article
    | Open Access

    Methylation levels of specific sites in the genome is correlated with aging. Here the authors develop a human-horse clock which could assist in translating anti-aging interventions from humans to horses and vice versa.

    • Steve Horvath
    • , Amin Haghani
    •  & Carrie J. Finno

  • Article
    | Open Access

    Whether G-quadruplexes (G4s) regulate stem cell self-renewal and fate determination during embryonic development is not well understood. Here, the authors reveal that the embryonic stem cell state is defined by very high G4 abundance. G4s are progressively lost during differentiation as cells transit to lower lineage potential while artificial G4 stabilisation leads to delayed differentiation.

    • Katherine G. Zyner
    • , Angela Simeone
    •  & Shankar Balasubramanian

  • Article
    | Open Access

    The human silencing hub (HUSH) complex, which includes TASOR, deposits repressive marks on HIV proviruses, resulting in gene repression. Here, Matkovic et al. show that TASOR interacts with RNA Polymerase II, predominantly under its elongating state, and RNA degradation proteins to repress HIV provirus expression.

    • Roy Matkovic
    • , Marina Morel
    •  & Florence Margottin-Goguet

  • Article
    | Open Access

    Microsatellite instability (MSI), caused by deficiency of the DNA mismatch repair system, has been associated with improved response to immune checkpoint blockade (ICB). Here the authors show that inactivation of protein phosphatase 2A induces a MSI status, promoting cytotoxic T cell infiltration and response to ICB in pre-clinical cancer models.

    • Yu-Ting Yen
    • , May Chien
    •  & Shih-Chieh Hung

  • Article
    | Open Access

    Mechanisms that underlie the progression of non-alcoholic fatty liver disease to the more severe non-alcoholic steatohepatitis are incompletely understood. Here the authors show that METTL3, a RNA methyltransferase that catalyzes mRNA m6 modifications, negatively regulates NASH progression via inhibiting the transcription of Cd36 and Ccl2.

    • Xinzhi Li
    • , Bingchuan Yuan
    •  & Zheng Chen

  • Article
    | Open Access

    m6A and m6Am are two prevalent mRNA modifications which are target for removal by the fat mass and obesity gene FTO. Here the authors capture the differential profile of these two modifications in the liver of obese mice and identify dynamic translation regulation by the m6Am modification.

    • Moshe Shay Ben-Haim
    • , Yishay Pinto
    •  & Gideon Rechavi

  • Article
    | Open Access

    Many genetic loci have been identified to be associated with kidney disease, but the molecular mechanisms are not well understood. Here, the authors perform epigenome-wide association studies on kidney function measures to identify epigenetic marks and pathways involved in kidney function.

    • Pascal Schlosser
    • , Adrienne Tin
    •  & Alexander Teumer

  • Article
    | Open Access

    Integrating functional data with GWAS loci can help interpret the function of genetic variants associated with disease. Here the authors map cis and trans methylation QTL in CD4 + T cells from patients and colocalize with GWAS loci in order to interpret genetic variants associated with multiple sclerosis.

    • Tina Roostaei
    • , Hans-Ulrich Klein
    •  & Philip L. De Jager

  • Article
    | Open Access

    How enhancers transition from a hypoacetylated primed state to a hyperacetylated-active state in response to differentiation stimuli is incompletely understood. Here the authors show that SETD5 forms a complex with NCoR-HDAC3 co-repressor to prevent histone acetylation of master adipogenic gene enhancers, while SETD5 degradation triggers enhancer hyperacetylation and transition to active state.

    • Yoshihiro Matsumura
    • , Ryo Ito
    •  & Juro Sakai

  • Article
    | Open Access

    Nucleosomes form arrays with even spacing between them in virtually all eukaryotes; however, their biogenesis is incompletely understood. Here the authors show that nucleosome density and DNA sequence along with the Ino80 chromatin remodeling complex play a role in nucleosome array formation in yeast and that the transcriptional machinery disrupts evenly-spaced nucleosomes.

    • Ashish Kumar Singh
    • , Tamás Schauer
    •  & Felix Mueller-Planitz

  • Article
    | Open Access

    Polycomb Repressive Complex 2, an important regulator of embryonic development, exists in two configurations, PRC2.1 and PRC2.2. Here the authors dissect the functional contributions of these two PRC2 subunits and observed complex-specific alterations in the cell state of pluripotent and early differentiating cells.

    • Chet H. Loh
    • , Siebe van Genesen
    •  & Gert Jan C. Veenstra

  • Article
    | Open Access

    The molecular origins of epialleles remain unknown. Here, the authors show that a positive feedback loop between H3K9me2 and CMT2/3 is a major contributing factor to the origins of spontaneous epialleles and that heterochromatin is a quantitative trait associated with spontaneous epiallele formation.

    • Yinwen Zhang
    • , Hosung Jang
    •  & Robert J. Schmitz

  • Article
    | Open Access

    Rhabdomyosarcoma (RMS) is a pediatric malignancy of skeletal muscle lineage with an aggressive subtype caused by translocations involving PAX3- /PAX7-FOXO1 chimeric transcription factors. Here the authors show that the BRG1-containing BAF complex is overexpressed and acts largely independently of the PAX3-FOXO1 chimera on chromatin to result in a myogenic differentiation blockade in this malignancy.

    • Dominik Laubscher
    • , Berkley E. Gryder
    •  & Javed Khan

  • Article
    | Open Access

    The molecular mechanisms that drive hematopoietic stem cell functional decline under conditions of telomere shortening are not completely understood. Here the authors demonstrate that hematopoietic stem cells with short telomeres induced by mutations affecting telomerase complex genes undergo differentiation towards megakaryopoiesis through the activation of the IFI16-mediated interferon response.

    • Natthakan Thongon
    • , Feiyang Ma
    •  & Simona Colla

  • Article
    | Open Access

    Dynamic changes in chromatin landscape affect CD8+ T cell phenotype and function in chronic infections and cancer. Here the authors show that targeting the histone demethylase LSD1 increases the persistence of progenitor exhausted CD8+ T cells, improving response to immune checkpoint blockade in preclinical cancer models.

    • Yi Liu
    • , Brian Debo
    •  & Yang Shi

  • Article
    | Open Access

    An upregulation of NSD2, a histone H3 lysine 36 (H3K36) methyltransferase is linked to multiple myeloma and other types of cancer. Here, the authors provide insights into the regulatory mechanism of NSD2 by determining the 2.8 Å cryo-EM structure of the NSD2 bound nucleosome complex, and based on MD simulations they discuss how two oncogenic mutations enhance NSD2 activity.

    • Ko Sato
    • , Amarjeet Kumar
    •  & Toru Sengoku

  • Article
    | Open Access

    The mammalian SWI/SNF nucleosome remodeler is required for spermatogenesis. Here, the authors show that PBAF is essential for meiotic cell division in males and required to activate the expression of critical genes involved in spindle assembly and nuclear division in spermatocytes.

    • Debashish U. Menon
    • , Oleksandr Kirsanov
    •  & Terry Magnuson

  • Article
    | Open Access

    Stochastic autosomal allele expression bias has been widely documented, yet the mechanisms behind this consequential phenomenon remain poorly understood. Here the authors show that the presence of introns greatly restricts monoallelic expression in a C. elegans model.

    • Bryan Sands
    • , Soo Yun
    •  & Alexander R. Mendenhall

  • Article
    | Open Access

    Muco-obstructive lung diseases are characterised by airway macrophage (AM) populations which may have epigenetic changes. Here using a mouse model the authors show epigenetic alteration of AMs with changes in LPS response, phagocytosis and efferocytosis similar to culture with mucus in vitro.

    • Joschka Hey
    • , Michelle Paulsen
    •  & Marcus A. Mall

  • Article
    | Open Access

    The effect of ATP-dependent chromatin remodelers on 3D genome organization has not been well studied. Here the authors employ in situ Hi-C with an auxin-inducible degron system to degrade chromatin remodelers in yeast to find that the 3D structure of chromatin collapses in their absence. The chromatin remodeling can modulate 3D architecture depending on chromosomal context and cell cycle stage.

    • Hyelim Jo
    • , Taemook Kim
    •  & Daeyoup Lee

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