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A map of cis-regulatory elements and 3D genome structures in zebrafish
A comprehensive map of transcriptomes, cis-regulatory elements, heterochromatin structure, the methylome and 3D genome organization in the zebrafish (Danio rerio) enables identification of species-specific and evolutionarily conserved regulatory features, and provides a foundation for modelling studies on human disease and development.
- Hongbo Yang
- , Yu Luan
- & Feng Yue
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Epigenetic gene silencing by heterochromatin primes fungal resistance
Fission yeast grown in sublethal levels of caffeine develop heterochromatin-dependent epimutations conferring unstable heritable gene silencing that conveys resistance to caffeine, while remaining genetically wild type.
- Sito Torres-Garcia
- , Imtiyaz Yaseen
- & Robin C. Allshire
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Dichotomous engagement of HDAC3 activity governs inflammatory responses
During the activation of mouse macrophages by lipopolysaccharides, histone deacetylase 3 controls inflammatory responses by both repressing and activating gene transcription depending on its differential association with transcription factors.
- Hoang C. B. Nguyen
- , Marine Adlanmerini
- & Mitchell A. Lazar
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Article
| Open AccessLandscape of cohesin-mediated chromatin loops in the human genome
A map of cohesin-mediated chromatin loops in 24 types of human cells identifies loops that show cell-type-specific variation, indicating that chromatin loops may help to specify cell-specific gene expression programs and functions.
- Fabian Grubert
- , Rohith Srivas
- & Michael Snyder
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Histone H3.3 phosphorylation amplifies stimulation-induced transcription
The histone variant H3.3 is phosphorylated at Ser31 in induced genes, and this selective mark stimulates the histone methyltransferase SETD2 and ejects the ZMYND11 repressor, thus revealing a role for histone phosphorylation in amplifying de novo transcription.
- Anja Armache
- , Shuang Yang
- & Steven Z. Josefowicz
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Article |
Wapl repression by Pax5 promotes V gene recombination by Igh loop extrusion
Pax5 regulates contraction of the immunoglobulin heavy chain (Igh) locus—an essential step in V(D)J recombination—by promoting chromatin loop extrusion via repression of Wapl expression.
- Louisa Hill
- , Anja Ebert
- & Meinrad Busslinger
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Nucleosome-bound SOX2 and SOX11 structures elucidate pioneer factor function
Cryo-electron microscopy structures of the DNA-binding domains of the pioneer transcription factor SOX2 and its close homologue SOX11 elucidate the role of these factors in initiating chromatin opening and nucleosome remodelling.
- Svetlana O. Dodonova
- , Fangjie Zhu
- & Patrick Cramer
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Cryo-EM structure of SWI/SNF complex bound to a nucleosome
The cryo-electron microscopy structure of the yeast SWI/SNF complex bound to a nucleosome substrate provides insights into the chromatin-remodelling function of this family of protein complexes and suggests mechanisms by which the mutated proteins may cause cancer.
- Yan Han
- , Alexis A Reyes
- & Yuan He
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Article |
Phase separation directs ubiquitination of gene-body nucleosomes
The yeast E3 ligase Bre1 forms a core–shell condensate with the scaffold protein Lge1, implicating liquid–liquid phase separation as a mechanism in the ubiquitination of histone H2B along gene bodies.
- Laura D. Gallego
- , Maren Schneider
- & Alwin Köhler
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Structure of SWI/SNF chromatin remodeller RSC bound to a nucleosome
The cryo-electron microscopy structure of the 16-subunit yeast SWI/SNF complex RSC in complex with a nucleosome substrate provides insights into the chromatin-remodelling function of this family of protein complexes.
- Felix R. Wagner
- , Christian Dienemann
- & Patrick Cramer
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Article |
Structure of the transcription coactivator SAGA
Structural studies on the yeast transcription coactivator complex SAGA (Spt–Ada–Gcn5–acetyltransferase) provide insights into the mechanism of initiation of regulated transcription by this multiprotein complex, which is conserved among eukaryotes.
- Haibo Wang
- , Christian Dienemann
- & Patrick Cramer
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Article |
Negative supercoil at gene boundaries modulates gene topology
The topoisomerase Top2 and the chromatin-binding protein Hmo1 maintain under-wound and over-wound DNA at different regions within a gene and thereby modulate the topology of genes.
- Yathish Jagadheesh Achar
- , Mohamood Adhil
- & Marco Foiani
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Article |
The structural basis for cohesin–CTCF-anchored loops
The crystal structure of the SA2–SCC1 subunits of human cohesin in complex with CTCF reveals the molecular basis of the cohesin–CTCF interaction that enables the dynamic regulation of chromatin folding.
- Yan Li
- , Judith H. I. Haarhuis
- & Daniel Panne
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H2A.Z facilitates licensing and activation of early replication origins
DNA replication in eukaryotes requires the histone variant H2A.Z, which binds the enzyme SUV420H1 to promote the dimethylation of histone H4, in turn recruiting the origin-recognition complex to activate early replication origins.
- Haizhen Long
- , Liwei Zhang
- & Guohong Li
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FACT caught in the act of manipulating the nucleosome
Two cryo-electron-microscopy images of the histone chaperone FACT interacting with components of nucleosomes shed light on how FACT manipulates nucleosomes to promote transcription, DNA repair and DNA replication.
- Yang Liu
- , Keda Zhou
- & Karolin Luger
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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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Stabilization of chromatin topology safeguards genome integrity
Super-resolution microscopy demonstrates how changes in the 3D organization of chromatin protect DNA against excessive degradation following damage.
- Fena Ochs
- , Gopal Karemore
- & Claudia Lukas
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Metabolic regulation of gene expression by histone lactylation
The lactylation of lysine residues on histones in mammalian cells is stimulated by hypoxia and bacterial challenges, and increased histone lactylation induces genes involved in wound healing.
- Di Zhang
- , Zhanyun Tang
- & Yingming Zhao
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Alcohol metabolism contributes to brain histone acetylation
Acetate that is produced from the breakdown of alcohol contributes to histone acetylation in the brain, indicating that there is a direct link between alcohol metabolism and gene expression.
- P. Mews
- , G. Egervari
- & S. L. Berger
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HP1 reshapes nucleosome core to promote phase separation of heterochromatin
The S. pombe HP1 protein Swi6 couples chromatin compaction to phase separation by dynamically exposing buried histone residues within nucleosomes.
- S. Sanulli
- , M. J. Trnka
- & G. J. Narlikar
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Letter |
The fundamental role of chromatin loop extrusion in physiological V(D)J recombination
V(D)J recombination in B cells involves cohesin-mediated extrusion of chromatin loops to present DNA targets for cleavage and joining.
- Yu Zhang
- , Xuefei Zhang
- & Frederick W. Alt
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Letter |
Structural basis of nucleosome recognition and modification by MLL methyltransferases
Cryo-electron microscopy structures of mixed-lineage leukaemia methyltransferases 1 and 3 associated with unmodified or mono-ubiquitinated nucleosome reveal the structural basis for the activity specificity and regulation of these enzymes.
- Han Xue
- , Tonghui Yao
- & Jing Huang
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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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Letter |
BORIS promotes chromatin regulatory interactions in treatment-resistant cancer cells
The CTCF paralogue BORIS is upregulated in transcriptionally reprogrammed neuroblastoma cells rendered resistant to targeted therapy, in which it promotes regulatory chromatin interactions that maintain the resistance phenotype.
- David N. Debruyne
- , Ruben Dries
- & Rani E. George
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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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Activation of PDGF pathway links LMNA mutation to dilated cardiomyopathy
A disease model using cardiomyocytes derived from induced pluripotent stem cells of patients with mutated LMNA-related dilated cardiomyopathy reveals that the abnormal activation of the PDGF pathway is associated with the arrhythmic phenotypes of patients.
- Jaecheol Lee
- , Vittavat Termglinchan
- & Joseph C. Wu
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Letter |
Heterochromatin drives compartmentalization of inverted and conventional nuclei
Attractions between heterochromatic regions are essential for phase separation of the active and inactive genome in inverted and conventional nuclei, whereas chromatin–lamina interactions are necessary to build the conventional genomic architecture from these segregated phases.
- Martin Falk
- , Yana Feodorova
- & Leonid A. Mirny
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DNA damage detection in nucleosomes involves DNA register shifting
Cryo-electron microscopy structures reveal that the DNA-repair factor UV-DDB exposes inaccessible nucleosome lesions for binding by inducing a translational shift in the nucleosome position.
- Syota Matsumoto
- , Simone Cavadini
- & Nicolas H. Thomä
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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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Review Article |
Transcription factors and 3D genome conformation in cell-fate decisions
Three-dimensional genome architecture has important roles in the regulation of gene expression and is therefore a key determinant of cell identity in normal development and in disease states.
- Ralph Stadhouders
- , Guillaume J. Filion
- & Thomas Graf
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Letter |
Sensory experience remodels genome architecture in neural circuit to drive motor learning
The authors identify a role for genome architecture reorganization in anterior dorsal cerebellar vermis granule neurons in learning a conditioned startle paradigm in mice.
- Tomoko Yamada
- , Yue Yang
- & Azad Bonni
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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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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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Article |
Visualizing DNA folding and RNA in embryos at single-cell resolution
Optical reconstruction of chromatin architecture and multiplex RNA labelling traces the DNA path in single cells and its relationship to transcription.
- Leslie J. Mateo
- , Sedona E. Murphy
- & Alistair N. Boettiger
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Letter |
Mechanism of DNA translocation underlying chromatin remodelling by Snf2
Cryo-EM structures of yeast Snf2 bound to the nucleosome in the presence of ADP or an ATP analogue reveal that Snf2 binding leads to distortion of the DNA, and a two-step mechanism underlying chromatin remodelling by Snf2 is proposed.
- Meijing Li
- , Xian Xia
- & Zhucheng Chen
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Letter |
Multiplex chromatin interactions with single-molecule precision
A strategy using droplet-based and barcode-linked sequencing captures multiplex chromatin interactions at single-molecule precision, and here provides topological insight into chromatin structures and transcription in Drosophila.
- Meizhen Zheng
- , Simon Zhongyuan Tian
- & Yijun Ruan
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Article |
LHX2- and LDB1-mediated trans interactions regulate olfactory receptor choice
Specific interchromosomal contacts in olfactory sensory neurons form a super-enhancer that controls the expression of a single olfactory receptor in each neuron.
- Kevin Monahan
- , Adan Horta
- & Stavros Lomvardas
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Letter
| Open AccessGenome organization and DNA accessibility control antigenic variation in trypanosomes
Long-read sequencing allows the assembly of antigen-gene arrays in Trypanosoma brucei and, coupled with deletion experiments, demonstrates that histone variants act as a molecular link between genome architecture, chromatin conformation and antigen variation.
- Laura S. M. Müller
- , Raúl O. Cosentino
- & T. Nicolai Siegel
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Article |
Transcription factor dimerization activates the p300 acetyltransferase
The activation of the histone acetyltransferase p300 depends on the activation and oligomerization status of transcription factor ligands.
- Esther Ortega
- , Srinivasan Rengachari
- & Daniel Panne
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Letter |
Principles of nucleosome organization revealed by single-cell micrococcal nuclease sequencing
Single-cell micrococcal nuclease sequencing simultaneously measures chromatin accessibility and genome-wide nucleosome positioning in single cells to reveal principles of nucleosome organization.
- Binbin Lai
- , Weiwu Gao
- & Keji Zhao
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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 |
Activity-dependent neuroprotective protein recruits HP1 and CHD4 to control lineage-specifying genes
ADNP interacts with the chromatin remodeller CHD4 and the heterochromatin protein HP1 to form a complex termed ChAHP that represses gene expression independently of the histone H3K9me3 modification.
- Veronika Ostapcuk
- , Fabio Mohn
- & Marc Bühler
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Letter |
Chromatin analysis in human early development reveals epigenetic transition during ZGA
By applying an optimized ATAC-seq protocol to human early embryos, distinct accessible chromatin landscapes are found before and after zygotic genome activation, revealing a marked epigenetic transition during zygotic genome activation and putative regulatory elements wiring human early development.
- Jingyi Wu
- , Jiawei Xu
- & Yingpu Sun
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Letter |
Structure and regulation of the human INO80–nucleosome complex
Cryo-electron microscopy structure of the human INO80 chromatin remodeller in complex with a bound nucleosome reveals that its motor domains are located at the DNA wrap around the histone core.
- Rafael Ayala
- , Oliver Willhoft
- & Xiaodong Zhang
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Letter |
Structural basis for ATP-dependent chromatin remodelling by the INO80 complex
Cryo-electron microscopy structures of the evolutionarily conserved core of a fungal INO80 complex bound to the nucleosomal substrate reveal the mechanism underlying nucleosome sliding and histone editing used by this ATP-dependent chromatin remodeller.
- Sebastian Eustermann
- , Kevin Schall
- & Karl-Peter Hopfner
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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 |
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 |
Promoter-bound METTL3 maintains myeloid leukaemia by m6A-dependent translation control
The methyltransferase METTL3 promotes the leukaemic state in acute myeloid leukaemia (AML) by catalysing the m6A RNA modification through its recruitment on the transcription start sites of AML-associated genes.
- Isaia Barbieri
- , Konstantinos Tzelepis
- & Tony Kouzarides
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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