Featured
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Outlook |
How plants and insects inherit immunity from their parents
Passing on short-term immunity to offspring is common in vertebrates, but plants and invertebrates take transgenerational immunity much further.
- Brian Owens
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Article |
Chromatin structure dynamics during the mitosis-to-G1 phase transition
Analysis of the dynamics of chromosome reorganization after exit from mitosis reveals the distinct but mutually influential forces that drive chromatin reconfiguration.
- Haoyue Zhang
- , Daniel J. Emerson
- & Gerd A. Blobel
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News & Views |
Histone lactylation links metabolism and gene regulation
Cells regulate gene expression in part through the chemical labelling of histone proteins. Discovery of a label derived from lactate molecules reveals a way in which cells link gene expression to nutrient metabolism.
- Luke T. Izzo
- & Kathryn E. Wellen
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Article |
Altered chromosomal topology drives oncogenic programs in SDH-deficient GISTs
Gastrointestinal stromal tumours can be initiated by gain-of-function mutations of the KIT or PDGFRA oncogenes but also by loss of the metabolic complex succinate dehydrogenase (SDH), which leads to DNA hypermethylation; this study shows that in SDH-deficient tumours, displacement of CTCF insulators by DNA methylation activates oncogene expression, illustrating how epigenetic alterations can drive oncogenic signalling in the absence of kinase mutations.
- William A. Flavahan
- , Yotam Drier
- & Bradley E. Bernstein
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Letter |
Coordinated alterations in RNA splicing and epigenetic regulation drive leukaemogenesis
Analyses of transcriptomes from patients with acute myeloid leukaemia identified frequently co-occurring mutations of IDH2 and SRSF2, which functional analyses showed to have distinct and coordinated leukaemogenic effects on the epigenome and RNA splicing.
- Akihide Yoshimi
- , Kuan-Ting Lin
- & Omar Abdel-Wahab
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News & Views |
A key to unlocking chromatin revealed by complex structures
Histone proteins pack DNA into a condensed form called chromatin. Detailed structures of the MLL family of histone-modifying protein complexes have been defined, shedding light on how they operate.
- Steven J. Gamblin
- & Jon R. Wilson
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Letter |
The histone mark H3K36me2 recruits DNMT3A and shapes the intergenic DNA methylation landscape
H3K36me2 targets DNMT3A to intergenic regions and this process, together with H3K36me3-mediated recruitment of DNMT3B, has a key role in establishing and maintaining genomic DNA methylation landscapes.
- Daniel N. Weinberg
- , Simon Papillon-Cavanagh
- & Chao Lu
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News & Views |
Inhibitory protein puts a lid on an epigenetic marker
Two reports examine how a protein complex that adds transcription-repressing marks to histone proteins is potently inhibited by the protein EZHIP during the maturation of sperm and egg cells and in a type of brain cancer.
- Sergi Aranda
- & Luciano Di Croce
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Review Article |
Advances in epigenetics link genetics to the environment and disease
The authors review recent advances and current debates in epigenetics, including how epigenetic mechanisms interact with genetic variation, ageing, disease and the environment.
- Giacomo Cavalli
- & Edith Heard
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Letter |
FOXA1 mutations alter pioneering activity, differentiation and prostate cancer phenotypes
Mutations in the transcription factor FOXA1 that are common in prostate cancer result in gain-of-function effects that promote changes in the differentiation of tumour cells.
- Elizabeth J. Adams
- , Wouter R. Karthaus
- & Charles L. Sawyers
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Letter |
Active chromatin marks drive spatial sequestration of heterochromatin in C. elegans nuclei
MRG-1 indirectly promotes anchoring of chromatin in differentiated intestinal cells in Caenorhabditis elegans by sequestering the histone acetyltransferase CBP-1/p300.
- Daphne S. Cabianca
- , Celia Muñoz-Jiménez
- & Susan M. Gasser
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Letter |
Epigenetic evolution and lineage histories of chronic lymphocytic leukaemia
A single-cell approach is used to follow the heritable stochastic changes to DNA methylation that occur in primary chronic lymphocytic leukaemia and healthy B cells, allowing the tracing of cell lineage histories and evolution during treatment with ibrutinib.
- Federico Gaiti
- , Ronan Chaligne
- & Dan A. Landau
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Letter |
Arabidopsis FLL2 promotes liquid–liquid phase separation of polyadenylation complexes
A genetic screen for factors required by the Arabidopsis RNA-binding protein FCA identifies FLL2 as necessary in the formation of FCA nuclear bodies, and thus a role for FLL2 in liquid–liquid phase separation.
- Xiaofeng Fang
- , Liang Wang
- & Caroline Dean
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Letter |
A vitamin-C-derived DNA modification catalysed by an algal TET homologue
An algal TET dioxygenase homologue, CMD1, uses vitamin C as a glycerol donor to modify 5-methylcytosine and helps to regulate gene transcription in response to high light levels.
- Jian-Huang Xue
- , Guo-Dong Chen
- & Guo-Liang Xu
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Letter |
Mammalian ISWI and SWI/SNF selectively mediate binding of distinct transcription factors
Genetic deletion of mammalian chromatin remodelling complexes reveals that ISWI and SWI/SNF are required for binding of specific transcription factors and that ISWI regulates nucleosome positioning and nuclear organization in stem cells.
- Darko Barisic
- , Michael B. Stadler
- & Dirk Schübeler
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News |
Astronaut twins study spots subtle genetic changes caused by space travel
Some initial effects of long-term spaceflight ebbed in the months after astronaut Scott Kelly returned to Earth.
- Alexandra Witze
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News & Views |
Genetic paradox explained by nonsense
Gene mutations that truncate the encoded protein can trigger the expression of related genes. The discovery of this compensatory response changes how we think about genetic studies in humans and model organisms.
- Miles F. Wilkinson
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Letter |
PTC-bearing mRNA elicits a genetic compensation response via Upf3a and COMPASS components
mRNA that contains a premature termination codon (PTC) triggers a genetic compensation response that involves both transcription of its homologous genes and degradation of the mutated transcript by the nonsense-mediated decay pathway.
- Zhipeng Ma
- , Peipei Zhu
- & Jun Chen
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Analysis |
The expanding landscape of ‘oncohistone’ mutations in human cancers
The characterization of missense histone mutations that occur across several cancer types provides insight into the potential role of these mutations in altering chromatin structure and potentially contributing to tumour development.
- Benjamin A. Nacev
- , Lijuan Feng
- & C. David Allis
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News & Views |
Modification of histone proteins by serotonin in the nucleus
The function of histone proteins can be modified through addition or removal of certain chemical groups. The addition of a serotonin molecule is a newly found histone modification that could influence gene expression.
- Marlene Cervantes
- & Paolo Sassone-Corsi
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Letter |
Histone H3 trimethylation at lysine 36 guides m6A RNA modification co-transcriptionally
METTL14 recognizes the trimethyl mark on lysine 36 of histone H3 that directs m6A modifications co-transcriptionally.
- Huilin Huang
- , Hengyou Weng
- & Jianjun Chen
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Letter |
Histone serotonylation is a permissive modification that enhances TFIID binding to H3K4me3
In serotonin-rich tissues, tissue transglutaminase 2 is able to attach serotonin to a glutamine residue in histone H3; this modification mediates permissive gene expression in these tissues.
- Lorna A. Farrelly
- , Robert E. Thompson
- & Ian Maze
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Letter |
Anti-tumour immunity controlled through mRNA m6A methylation and YTHDF1 in dendritic cells
The m6A reader protein YTHDF1 suppresses the clearance of tumour cells by enhancing the translation of lysosomal proteases in dendritic cells and thereby suppressing tumour antigen presentation.
- Dali Han
- , Jun Liu
- & Chuan He
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News |
Gaps in our genes are more important than we thought
Introns, the bits of non-coding DNA scattered through our genes, may play an important role in cell survival
- Shamini Bundell
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News |
Cancer researchers seek to harness mysterious DNA ‘super-enhancers’
Whether DNA segments that amplify gene activity represent a previously unrecognized form of gene regulation is still under debate.
- Heidi Ledford
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Letter |
Stella safeguards the oocyte methylome by preventing de novo methylation mediated by DNMT1
Stella, a factor essential for female fertility, protects the oocyte methylome in mice by suppressing de novo DNA methylation mediated by the DNA methyltransferase DNMT1.
- Yingfeng Li
- , Zhuqiang Zhang
- & Bing Zhu
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News |
Healthy mice from same-sex parents have their own pups
Advance reveals genetic factors that require mammals to reproduce using two sexes.
- Jeremy Rehm
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Article |
Extensive sex differences at the initiation of genetic recombination
Differential DNA methylation and the long-range effects of chromatin organization lead to pronounced differences in recombination landscape between males and females.
- Kevin Brick
- , Sarah Thibault-Sennett
- & Galina V. Petukhova
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Letter |
Inhibitors of histone acetyltransferases KAT6A/B induce senescence and arrest tumour growth
Selective inhibitors of KAT6A and KAT6B inhibit MYST-catalysed histone acetylation, induce cell cycle exit and cellular senescence without causing DNA damage, and arrest lymphoma progression in mouse models.
- Jonathan B. Baell
- , David J. Leaver
- & Tim Thomas
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Letter |
Automethylation-induced conformational switch in Clr4 (Suv39h) maintains epigenetic stability
An autoinhibitory conformation of the histone H3K9 methyltransferase Clr4 of Schizosaccharomyces pombe helps to prevent aberrant heterochromatin formation and maintains epigenetic stability.
- Nahid Iglesias
- , Mark A. Currie
- & Danesh Moazed
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Letter |
Glucose-regulated phosphorylation of TET2 by AMPK reveals a pathway linking diabetes to cancer
Modulation of DNA 5-hydroxymethylcytosine by glucose reveals an AMPK–TET2–5hmC axis that links diabetes to cancer.
- Di Wu
- , Di Hu
- & Yujiang Geno Shi
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Letter |
Epigenetic inheritance mediated by coupling of RNAi and histone H3K9 methylation
In Schizosaccharomyces pombe, histone H3K9 methylation acts synergistically with short interfering RNA to perpetuate gene silencing during multiple mitotic and meiotic cell divisions.
- Ruby Yu
- , Xiaoyi Wang
- & Danesh Moazed
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Books & Arts |
Heredity beyond the gene
Nick Lane relishes Carl Zimmer’s history of inherited traits in all their messiness, from genes and culture to epigenetics.
- Nick Lane
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Article |
Spatiotemporal regulation of liquid-like condensates in epigenetic inheritance
ZNFX-1 and WAGO-4 localize to germ granules in early Caenorhabditis elegans embryogenesis and later separate to form independent liquid-like droplets, and the temporal and spatial ordering of these droplets may help cells to organize complex RNA processing pathways.
- Gang Wan
- , Brandon D. Fields
- & Scott Kennedy
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News & Views |
Pancreatic cancer foiled by a switch of tumour subtype
Mutations in the gene KDM6A drive an aggressive subtype of pancreatic cancer by causing repositioning of an enzyme complex that modifies histone proteins associated with DNA, leading to altered gene expression.
- Fieke Froeling
- & David Tuveson
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Letter |
Pluripotency factors functionally premark cell-type-restricted enhancers in ES cells
Binding of an embryonic stem in two cases cell-specific transcription factor pre-marks cell-type-restricted enhancers in embryonic stem in two cases cells, and this premarking is required for the robustness of enhancer activation in differentiated cells.
- Hong Sook Kim
- , Yuliang Tan
- & Michael G. Rosenfeld
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Letter |
The cis-regulatory dynamics of embryonic development at single-cell resolution
An improved assay for chromatin accessibility at single-cell resolution in Drosophila melanogaster embryos enables identification of developmental-stage- and cell-lineage-specific patterns of chromatin-level transcriptional regulation.
- Darren A. Cusanovich
- , James P. Reddington
- & Eileen E. M. Furlong
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Letter |
Epigenetic reprogramming enables the transition from primordial germ cell to gonocyte
Gonadal germline epigenetic reprogramming involves an interplay between DNA methylation, the polycomb complex and Tet1 in both DNA methylation dependent and independent roles, to ensure the activation of a specific subset of genes critical for progression of gametogenesis.
- Peter W. S. Hill
- , Harry G. Leitch
- & Petra Hajkova
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Letter |
Structural basis for DNMT3A-mediated de novo DNA methylation
A crystal structure of DNMT3A and its regulatory partner DNMT3L bound to DNA reveals the mechanistic basis for DNMT3A-mediated DNA methylation and establishes its aetiological link to human disease.
- Zhi-Min Zhang
- , Rui Lu
- & Jikui Song
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Letter |
A Myc enhancer cluster regulates normal and leukaemic haematopoietic stem cell hierarchies
A blood enhancer cluster forms a highly combinatorial system that allows precise control of Myc expression across normal and leukaemic haematopoietic stem-cell hierarchies.
- Carsten Bahr
- , Lisa von Paleske
- & François Spitz
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News & Views |
Tumour lymph vessels boost immunotherapy
A high level of expression of the growth-factor protein VEGF-C is associated with tumours that have extensive lymph vessels and poor prognosis. It emerges that such tumours are highly susceptible to immunotherapy.
- Christine Moussion
- & Shannon J. Turley
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Letter |
Selective silencing of euchromatic L1s revealed by genome-wide screens for L1 regulators
The retrotransposition of L1 is controlled by functionally diverse genes at the transcriptional or post-transcriptional levels, and its silencing can lead to the downregulation of host gene expression.
- Nian Liu
- , Cameron H. Lee
- & Joanna Wysocka
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Letter |
KAT2A coupled with the α-KGDH complex acts as a histone H3 succinyltransferase
The histone acetyl transferase KAT2A (also known as GCN5) can also catalyse histone succinylation, with the α-KGDH complex providing a local source of succinyl-CoA.
- Yugang Wang
- , Yusong R. Guo
- & Zhimin Lu
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Letter |
BCAT1 restricts αKG levels in AML stem cells leading to IDHmut-like DNA hypermethylation
The mechanistic basis for the role of the metabolic enzyme BCAA transaminase 1 (BCAT1) in acute myeloid leukaemias.
- Simon Raffel
- , Mattia Falcone
- & Andreas Trumpp
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Inside View |
Inside View: Bettencourt Schueller Foundation
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News & Views |
Layered-up regulation in the developing brain
Modification of messenger RNAs through a process called m6A methylation facilitates dynamic temporal regulation of RNA levels in neural precursor cells, enabling fine-tuning of developing neuronal circuits in the brain.
- J. David Sweatt
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Letter |
Embryonic epigenetic reprogramming by a pioneer transcription factor in plants
The seed-specific transcription factor LEC1 promotes an active chromatin state at the floral repressor FLC and activates its expression in the Arabidopsis pro-embryo, thus reversing the winter cold-induced silenced state that is inherited from gametes.
- Zeng Tao
- , Lisha Shen
- & Yuehui He
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Letter
| Open Access
Landscape of X chromosome inactivation across human tissues
Multiple transcriptome approaches, including single-cell sequencing, demonstrate that escape from X chromosome inactivation is widespread and occasionally variable between cells, chromosomes, and tissues, resulting in sex-biased expression of at least 60 genes and potentially contributing to sex-specific differences in health and disease.
- Taru Tukiainen
- , Alexandra-Chloé Villani
- & Daniel G. MacArthur
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Letter |
Radically truncated MeCP2 rescues Rett syndrome-like neurological defects
Analysis of the minimal functional unit for MeCP2 protein shows that its function is to recruit the NCoR/SMRT co-repressor complex to methylated sites on chromatin, which may have use in designing strategies for gene therapy of Rett syndrome.
- Rebekah Tillotson
- , Jim Selfridge
- & Adrian Bird
Developmental ROS individualizes organismal stress resistance and lifespan