Histone variants articles within Nature Communications

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  • Article
    | Open Access

    Eviction of histones from nucleosomes and their exchange with newly synthesized or alternative variants is a central epigenetic determinant. Here the authors implement a molecular sensor that reports on steady-state exchange of histones in mESC and mice revealing dependency between deposition of histone variant H3.3 and exchange of H3.1 and H2B in both open and closed chromatin.

    • Marko Dunjić
    • , Felix Jonas
    •  & Yonatan Stelzer
  • Article
    | Open Access

    The chromatin remodeling complex ATRX can promote gene expression, for example by binding G-quadruplexes (G4s) to prevent their negative effect on expression. Here the authors use a single-cell approach to show that only a subset of erythroid cells isolated from patients with ATRX mutations have reduced chromatin accessibility and alpha globin expression, suggesting a stochastic process.

    • Julia Truch
    • , Damien J. Downes
    •  & Richard J. Gibbons
  • Article
    | Open Access

    During embryogenesis, the genome becomes transcriptionally active in a process known as zygotic genome activation (ZGA); how ZGA is initiated is still an open question. Here the authors show histone variant H2A.Z deposition precedes RNA polymerase II binding on chromatin, before ZGA. H2A.Z loss causes transcriptional downregulation of ZGA genes and leads to changes in the 3D genome organization.

    • Dafne Ibarra-Morales
    • , Michael Rauer
    •  & Nicola Iovino
  • Article
    | Open Access

    Endogenous retroviruses (ERVs) compose a significant portion of mammalian genomes; however, how ERVs are regulated is not well known. Here the authors performed a genome-wide sgRNA screen to identify Morc3 as a mediator of ERV silencing. They show Morc3 associates with the H3.3 chaperone Daxx, and that loss of Morc3 leads to reduced H3.3 at ERVs.

    • Sophia Groh
    • , Anna Viktoria Milton
    •  & Gunnar Schotta
  • Article
    | Open Access

    ATRX is a chromatin remodeling protein, which loss has been associated to replication stress, DNA damage, and DNA repair failures that drive genome instability. Here the authors reveal that ATRX protects genomic integrity at G4-containing regions by maintaining these regions in a closed heterochromatic state.

    • Yu-Ching Teng
    • , Aishwarya Sundaresan
    •  & Laura A. Banaszynski
  • Article
    | Open Access

    The epigenetic mechanisms coordinating the maintenance of adult cellular lineages remain poorly understood. Here the authors demonstrate that HIRA, a H3.3 histone chaperone, establishes the chromatin landscape required for skeletal muscle cell identity.

    • Joana Esteves de Lima
    • , Reem Bou Akar
    •  & Frédéric Relaix
  • 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

    Alternative Lengthening of Telomeres (ALT) is a telomere maintenance pathway utilised in 15% of cancers that have been associated with mutations in ATRX. Here the authors reveal a functional role of histone demethylases KDM4B in regulating ALT activation.

    • M. Udugama
    • , L. Hii
    •  & L. H. Wong
  • Article
    | Open Access

    Histone variant H2A.Z has been suggested to contribute to the regulation of promoter accessibility. Here, the authors present high-depth maps of the position and accessibility of H2A.Z-containing nucleosomes for human Pol II promoters and provide evidence that H2A.Z has multiple and distinct roles in regulating gene expression dependent upon its location in a promoter.

    • Lauren Cole
    • , Sebastian Kurscheid
    •  & David J. Tremethick
  • Article
    | Open Access

    The order of DNA methylation and histone modifications during transcription remained unclear. Here the authors show that HMGA2 induces DNA nicks at TGFB1-responsive genes, promoting nucleosome incorporation containing γ-H2AX, which is required for repair-mediated DNA demethylation and transcription.

    • Stephanie Dobersch
    • , Karla Rubio
    •  & Guillermo Barreto
  • Article
    | Open Access

    Chromatin state underlies cellular function, and transcription factor binding patterns along with epigenetic marks define chromatin state. Here the authors show that the histone chaperone ANP32E functions through regulation of H2A.Z to restrict genome-wide chromatin accessibility and to inhibit gene transcriptional activation.

    • Kristin E. Murphy
    • , Fanju W. Meng
    •  & Patrick J. Murphy
  • Article
    | Open Access

    Histone ubiquitination plays a critical role in the DNA damage response pathway. Here the authors reveal how RNF168 ubiquitinates the H2A family including noncanonical variants, H2AZ and macroH2A1/2, at the divergent N-terminal tail lysine residue.

    • Jessica L. Kelliher
    • , Kirk L. West
    •  & Justin W. C. Leung
  • Article
    | Open Access

    Histone modification and deposition are key regulators of transcription. Here, Kraus et al. provide a quantitative histone acetylome for Trypanosoma brucei, identify histone modifications enriched at transcription start sites, and show how H4 and H2A.Z acetylation affect histone deposition and transcription in trypanosomes.

    • Amelie J. Kraus
    • , Jens T. Vanselow
    •  & T. Nicolai Siegel
  • Article
    | Open Access

    The poly(ADP-ribose) polymerases play a key role in maintaining genomic integrity by detecting DNA damage and mediating repair. Here the authors characterize the kinetics of PARP1 binding to a variety of nucleosomes harbouring DNA double-strand breaks.

    • Deepti Sharma
    • , Louis De Falco
    •  & Curt A. Davey
  • Article
    | Open Access

    Substitution of lysine 27 with methionine in histone H3.3 (H3.3K27M) is a driver mutation of pediatric high-grade gliomas. Here the authors show that H3.3K27M-mediated alterations in H3K27me3 distribution result in ectopic DNA replication and cell cycle progression of germ cells in Caenorhabditis elegans, through JNK pathway misregulation.

    • Kamila Delaney
    • , Maude Strobino
    •  & Florian A. Steiner
  • Article
    | Open Access

    Although the centromere-specific histone CENP-A usually assembles on specific genomic sequences, centromeric DNA is not conserved. Here the authors characterize the genome and centromeres of related fission yeasts and provide evidence that Schizosaccharomyces centromere DNA possesses intrinsic conserved properties that promote assembly of CENP-A chromatin.

    • Pin Tong
    • , Alison L. Pidoux
    •  & Robin C. Allshire
  • Article
    | Open Access

    CENP-A histone variants replace histones H3 at centromeres. Here the authors use a single-chain antibody fragment (scFv) to stabilize human CENP-A nucleosome containing a native α-satellite DNA and solved its structure by cryo-EM to 2.6 Å resolution, providing insight into the structure and function of the CENP-A nucleosome.

    • Bing-Rui Zhou
    • , K. N. Sathish Yadav
    •  & Ping Zhang
  • Article
    | Open Access

    Lgr5+ stem cells in intestinal crypts are critical for gut epithelium homeostasis. Here, the authors show that Znht1 critically regulates intestinal homeostasis by promoting interaction between histone variant H2A.Z and its chaperone YL1 to incorporate H2A.Z into genes involved in intestinal stem cell fate.

    • Bing Zhao
    • , Ying Chen
    •  & Xinhua Lin
  • Article
    | Open Access

    Kinetochore function depends on H4K20 monomethylation in centromeric nucleosomes but the underlying mechanism is unclear. Here, the authors provide evidence that the centromere-specific nucleosome subunit CENP-A facilitates H4K20 methylation by enabling a conformational change of the H4 N-terminal tail.

    • Yasuhiro Arimura
    • , Hiroaki Tachiwana
    •  & Hitoshi Kurumizaka
  • Article
    | Open Access

    The histone variant macroH2A1 localizes to two functionally distinct chromatin subtypes marked by either H3K27me3 or H2B acetylations. Here the authors identify the features of macroH2A1 required for its recruitment to H2B-acetylated chromatin and identify H2BK20 acetylation as a critical requirement for this recruitment.

    • Penelope D. Ruiz
    •  & Matthew J. Gamble
  • 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

    Recent studies have identified a number of oncogenic histone point mutations in different cancers. Here the authors provide evidence that H3.3 G34R substitution mutation, which is found in paediatric gliomas, causes changes in H3K9me3 and H3K36me3 by interfering with the KDM4 family of K9/K36 demethylases.

    • Hsiao P. J. Voon
    • , Maheshi Udugama
    •  & Lee H. Wong
  • Article
    | Open Access

    Diffuse intrinsic pontine gliomas exhibit a characteristic mutation of lysine 27 to methionine (K27M) in genes encoding histone H3.3. Here the authors show that the H3.3K27M mutation imposes a specific pattern of H3.3K27 methylation by altering the target search dynamics of PcG proteins.

    • Roubina Tatavosian
    • , Huy Nguyen Duc
    •  & Xiaojun Ren
  • Article
    | Open Access

    Histone variant H3.3 is incorporated at transcriptionally active genes and is associated with active marks. Here, the authors investigate H3.3 deposition during reprogramming and find that initially H3.3 helps maintain parental cell fate and is later required for establishment of the cell lineages.

    • Hai-Tong Fang
    • , Chadi A. EL Farran
    •  & Yuin-Han Loh
  • Article
    | Open Access

    Ubiquitylation of H2B is associated with transcription and regulation of chromatin structure. Here, the authors perform an unbiased screen to identify the role of chromatin modifications on ubiquitylation of H2BK120 and characterize the crosstalk between H2BK120ub and H2A modifications and variants.

    • Felix Wojcik
    • , Geoffrey P. Dann
    •  & Tom W. Muir
  • Article
    | Open Access

    Epigenome editing by zinc finger (ZF) and CRISPR-dCas9 technologies can induce or repress gene expression. Here, the authors show that histone methyltransferase PRDM9 fused to either dCas9 or ZF proteins can sustain gene re-expression, and H3K79me is required for stable gene re-expression.

    • David Cano-Rodriguez
    • , Rutger A F. Gjaltema
    •  & Marianne G Rots
  • Article
    | Open Access

    The histone H2A variants are involved in DNA repair, gene regulation and cancer development. In this study, the authors unravel an additional role for H2A.X in the regulation of mesenchymal-like traits and activation of the EMT transcription factors, Slug and ZEB1, in colon cancer cells.

    • Urbain Weyemi
    • , Christophe E. Redon
    •  & William M. Bonner
  • Article |

    INO80-C and SWR-C are chromatin remodelling enzymes with roles in transcription pathways. Here, the authors show that they both have similar architectures displaying a ‘tail’ domain and a heterohexameric ‘head’ domain, with conformational changes influencing nucleosomal binding and enzyme activity.

    • Shinya Watanabe
    • , Dongyan Tan
    •  & Craig L. Peterson
  • Article |

    Cellular senescence involves extensive structural changes to chromatin, but the role of histone variants and histone cleavage is unknown. Here, Duarte et al.identify histone variant H3.3 and its proteolytically processed form lacking a portion of the N-terminal tail as key regulators of senescence.

    • Luis F. Duarte
    • , Andrew R. J. Young
    •  & Emily Bernstein
  • Article |

    Chromatin templates can act as barriers against cellular reprogramming. Gaspar-Maia and colleagues use mouse models deficient in the histone variants macroH2A1 and macroH2A2, and find that macroH2A functions as an epigenetic barrier against induced pluripotency by silencing Utx target genes.

    • Alexandre Gaspar-Maia
    • , Zulekha A. Qadeer
    •  & Emily Bernstein