Chromatin

  • Article
    | Open Access

    CTCF is as an architectural protein involved in 3D genome folding; however its contribution to animal development has not been well characterized. Here the authors show that CTCF is not only pivotal for 3D chromatin structure and enhancer-promoter interactions in zebrafish, but it is also essential for controlling the expression of thousands of genes during development.

    • Martin Franke
    • , Elisa De la Calle-Mustienes
    •  & José L. Gómez-Skarmeta
  • Article
    | Open Access

    Polycomb repressive complexes (PRC1 and PRC2) repress genes that are crucial for development via epigenetic modifications; however, their role in differentiation is not well known. Here the authors reveal that a PCGF1-containing PRC1 variant facilitates exit from pluripotency by downregulating target genes and recruiting PRC2.

    • Hiroki Sugishita
    • , Takashi Kondo
    •  & Haruhiko Koseki
  • Article
    | Open Access

    β-actin loss can affect gene expression and heterochromatin organization. Here the authors conduct a comprehensive genomic analysis of β-actin knockout mouse embryonic fibroblasts (MEFs) to investigate the impact of changes in β-actin levels on 3d genome architecture and chromatin remodeling activities of BAF and polycomb proteins.

    • Syed Raza Mahmood
    • , Xin Xie
    •  & Piergiorgio Percipalle
  • Article
    | Open Access

    How cells coordinate chromatin dynamics with the cell cycle machinery to promote genome duplication during S phase is still a matter of study. Here the authors reveal by in vitro reconstitution assays that the AAA + -ATPase containing Yta7 protein in S. cerevisiae promotes chromatin.

    • Erika Chacin
    • , Priyanka Bansal
    •  & Christoph F. Kurat
  • Article
    | Open Access

    Although the interactors of pluripotency factors have been identified in mouse embryonic stem cells (ESCs), their interactors in human ESCs remain unexplored. Here the authors map OCT4 protein interactions in naïve and primed human ESCs to find specific interactions with BAF subunits that promote an open chromatin architecture at blastocyst-associated genes and ectodermal genes, respectively.

    • Xin Huang
    • , Kyoung-mi Park
    •  & Thorold W. Theunissen
  • Article
    | Open Access

    The effect of histone H4 lysine 20 methylation (H4K20me) on chromatin accessibility are not well established. Here the authors show how H4K20 methylation regulates chromatin structure and accessibility to ensure precise transcriptional outputs through the cell cycle using genome-wide approaches, in vitro biophysical assays, and NMR.

    • Muhammad Shoaib
    • , Qinming Chen
    •  & Claus S. Sørensen
  • Article
    | Open Access

    Proximity biotinylation is a powerful tool to profile interactomes, but it requires genetic engineering of the target protein. Here, the authors develop a proximity biotinylation enzyme that can be directed to the target using antibodies, enabling interactome profiling of endogenous proteins or PTMs.

    • Irene Santos-Barriopedro
    • , Guido van Mierlo
    •  & Michiel Vermeulen
  • Article
    | Open Access

    Mesomelic dysplasia, a severe shortening and bending of the limb, has been linked to rearrangements in the HoxD cluster in humans and mice. Here the authors engineer a 1 Mb inversion including the HoxD gene cluster and use this model to provide a mechanistic framework to understand and unify the molecular origins of human mesomelic dysplasia associated with 2q31.

    • Christopher Chase Bolt
    • , Lucille Lopez-Delisle
    •  & Denis Duboule
  • Article
    | Open Access

    Embryos at the 2-cell (2C) stage are totipotent, and overexpression of Dux transcription factor convert embryonic stem cells (ESCs) to a 2C-like state. Here the authors show that DUX-mediated 2C-like reprogramming is associated with DNA damage at CTCF sites and CTCF depletion promotes 2Clike conversion.

    • Teresa Olbrich
    • , Maria Vega-Sendino
    •  & Sergio Ruiz
  • Article
    | Open Access

    The polycomb repressive complex 2 (PRC2) is a histone methyltransferase regulating cell differentiation and identity. Here, the authors show that the vertebrate-specific PRC2 accessory subunit PALI1 facilitates substrate binding by the complex and elucidate the allosteric mechanism of PALI1- mediated PRC2 activation.

    • Qi Zhang
    • , Samuel C. Agius
    •  & Chen Davidovich
  • Article
    | Open Access

    Globin loci harbor genes that are expressed embryonically and silenced postnatally. Here the authors show that zeta-globin silencing depends upon selective hypoacetylation of its TAD subdomain, which blocks its interaction with the alpha-globin super-enhancer, and zeta-globin can be reactivated by acetylation.

    • Andrew J. King
    • , Duantida Songdej
    •  & Christian Babbs
  • Article
    | Open Access

    MORC ATPases are required for transposable element silencing and heterochromatin condensation in plants and animals. Here the authors show that Arabidopsis MORCs colocalize with sites of RNA-directed DNA methylation and provide evidence that they act as molecular tethers to efficiently establish DNA methylation.

    • Yan Xue
    • , Zhenhui Zhong
    •  & Steven E. Jacobsen
  • Article
    | Open Access

    Transcriptional state plays a role in genome organization, however factors that link these processes are not well known. Here, the authors show Drosophila transcription factor Motif 1-binding protein (M1BP) interacts with the insulator protein CP190 to promote insulator function and activate Motif 1-dependent transcription at topologically associating domain (TAD) borders.

    • Indira Bag
    • , Shue Chen
    •  & Elissa P. Lei
  • Article
    | Open Access

    Few studies have provided functional analysis of the epigenetic landscape in the regenerating liver. Here the authors define chromatin states in the quiescent vs. regenerating mouse liver through integration of genome wide profiles of DNA methylation, histone modifications, and chromatin accessibility, identifying H3K27me3 as an epigenetic mark conferring regenerative potential.

    • Chi Zhang
    • , Filippo Macchi
    •  & Kirsten C. Sadler
  • Article
    | Open Access

    The oncogenic chromatin remodeler ALC1 (amplification in liver cancer 1), also known as CHD1L is an ATP-dependent chromatin remodeler that relaxes chromatin and plays an important role in the poly(ADP-ribose) polymerase 1 -mediated DNA repair pathway. Here, the authors present the ALC1 crystal structure and a cryo-EM structure of ALC1 bound to a nucleosome, which reveal that ALC1 is autoinhibited and how it becomes activated.

    • Li Wang
    • , Kangjing Chen
    •  & Zhucheng Chen
  • Article
    | Open Access

    The cellular heterogeneity in brain obscures the identification of robust cellular regulatory networks. Here the authors integrate genome-wide chromosome conformation data from sorted neurons and glia, with transcriptomic and enhancer profiles, to characterize cell-type-specific gene regulatory landscapes in the human brain, and provide insights into cell-type-specific gene regulatory networks in brain disorders.

    • Benxia Hu
    • , Hyejung Won
    •  & Daniel H. Geschwind
  • 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

    How gene expression reactivation is promoted following DNA damage is not yet clear. Here, the authors identify a role for the human histone chaperone complex HIRA in transcription restart following UV damage independently of its function in new H3.3 histone deposition.

    • Déborah Bouvier
    • , Juliette Ferrand
    •  & Sophie E. Polo
  • Article
    | Open Access

    BRCA1-mediated resolution of R-loops has previously been described. Here the authors reveal a functional association of BRCA1 with TERRA RNA at telomeres, which develops in an R-loop-, and a cell cycle-dependent manner.

    • Jekaterina Vohhodina
    • , Liana J. Goehring
    •  & David M. Livingston
  • Article
    | Open Access

    While the role of specific posttranslational modifications (PTMs) is increasingly well understood for core histones, this is not the case for linker histone H1. Here the authors show that site-specific ubiquitylation of H1 results in distinct interactomes, regulates phase separation, and modulates assembly of chromatosomes.

    • Eva Höllmüller
    • , Simon Geigges
    •  & Florian Stengel
  • Article
    | Open Access

    Both A/B compartments and TADs are thought to be absent from the inactive X chromosome, but to be re-established with transcriptional reactivation and chromatin opening during X-reactivation. Here, the authors characterise gene reactivation, chromatin opening and chromosome topology during X-reactivation, observe A/B-like compartments on the inactive X that guide TAD formation independently of transcription during X-reactivation.

    • Moritz Bauer
    • , Enrique Vidal
    •  & Bernhard Payer
  • 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

    Existing studies of the chromatin accessibility, the primary mark of regulatory DNA, in Arabidopsis are based mainly on bulk samples. Here, the authors report the regulatory landscape of Arabidopsis thaliana roots at single-cell resolution.

    • Michael W. Dorrity
    • , Cristina M. Alexandre
    •  & Josh T. Cuperus
  • Article
    | Open Access

    Although chromatin remodelers have been shown to align nucleosome arrays to barriers and to generate spacing regularity among nucleosomes within arrays, it has remained unclear how the distance to barrier and the spacing length are determined in absolute terms. Here, the authors reveal that remodelers contain a ‘ruler’ element that sets remodeler-specific alignment and spacing distances when generating nucleosome arrays.

    • Elisa Oberbeckmann
    • , Vanessa Niebauer
    •  & Philipp Korber
  • Article
    | Open Access

    DNA sequence preferences or statistical positioning of histones has not explained genomic patterns of nucleosome organisation in vivo. Here, the authors establish DNA shape/mechanics as key elements that have evolved together with binding sites of DNA sequence-specific barriers so that such information directs nucleosome positioning by chromatin remodelers.

    • Elisa Oberbeckmann
    • , Nils Krietenstein
    •  & Sebastian Eustermann
  • Article
    | Open Access

    Multi-layered epigenetic regulation in higher eukaryotes makes it challenging to disentangle the individual effects of modifications on chromatin structure and function. Here, the authors expressed mammalian DNA methyltransferases in yeast, which have no DNA methylation, to show that methylation has intrinsic effects on chromatin structure.

    • Diana Buitrago
    • , Mireia Labrador
    •  & Modesto Orozco
  • Article
    | Open Access

    Resolving nucleosomes with chemical accuracy inside sub-Mb chromatin provides molecular insight into the modulation of chromatin structure and its liquid–liquid phase separation (LLPS). By developing a multiscale chromatin model, the authors find that DNA breathing enhances the valency, heterogeneity, and dynamics of nucleosomes, promoting disordered folding and LLPS.

    • Stephen E. Farr
    • , Esmae J. Woods
    •  & Rosana Collepardo-Guevara
  • 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

    Nucleosomes tightly wrap ~147 DNA base pairs around an octamer of histone proteins, but how nucleosome structural dynamics affect genome functioning is not completely clear. Here authors employ all-atom molecular dynamics simulations of nucleosome core particles and observe that octamer dynamics and plasticity enable DNA unwrapping and sliding.

    • Grigoriy A. Armeev
    • , Anastasiia S. Kniazeva
    •  & Alexey K. Shaytan
  • Article
    | Open Access

    PU.1 is a master regulator of myeloid development but its role in disease-relevant neutrophils is not well known. Here, the authors look at primary neutrophils from a human population and find that genetic variants affecting binding of PU.1 are associated with cell count and disease susceptibility.

    • Stephen Watt
    • , Louella Vasquez
    •  & Nicole Soranzo
  • Article
    | Open Access

    Acheiropodia is associated with homozygous deletions in the LMBR1 gene around ZRS, an enhancer regulating SHH during limb development, but how these deletions lead to this phenotype is unknown. Here the authors use whole-genome sequencing, ChIP-seq, 4C-seq and DNA FISH to show that alterations in CTCF motifs are responsible via altered enhancer–promoter interactions.

    • Aki Ushiki
    • , Yichi Zhang
    •  & Nadav Ahituv
  • Article
    | Open Access

    The role of transcriptional enhancers and 3D chromatin organisation in coordinating the transition from naive to primed pluripotency remains poorly understood. Here the authors generate a high-resolution atlas of gene regulatory interactions, chromatin profiles and transcription factor occupancy in naive and primed human pluripotent stem cells to provide insights into these developmental processes.

    • Peter Chovanec
    • , Amanda J. Collier
    •  & Peter J. Rugg-Gunn
  • Article
    | Open Access

    During development, H3K27me3 is reallocated from large domains in preimplantation embryos to mark promoters of developmental genes. Here the authors show that the deubiquitinase Usp9x interacts with, deubiquitinates and stabilizes PRC2 and provide evidence that a Usp9x-PRC2 regulatory axis is critical at peri-implantation.

    • Trisha A. Macrae
    •  & Miguel Ramalho-Santos
  • Article
    | Open Access

    Biogenesis of small nucleolar RNAs ribonucleoproteins (snoRNPs) requires dedicated assembly machinery. Here, the authors show that a subset of snoRNP assembly factors interacts, genetically or directly, with factors modulating chromatin architecture, suggesting a link between ribosome formation and chromatin functions.

    • Benoît Bragantini
    • , Christophe Charron
    •  & Bruno Charpentier
  • Article
    | Open Access

    G-quadruplexes (G4) can be formed from DNA sequences containing consecutive guanines organized in 4-interspaced tandem repeats. Here the authors reveal the association between G4 structures present at specific loci in Alzheimer’s disease neurons and reduced gene expression and perturbed alternative splicing.

    • Roy Hanna
    • , Anthony Flamier
    •  & Gilbert Bernier
  • Article
    | Open Access

    Chromosome segregation requires the association of the kinetochore protein complex with a specialized nucleosome at the centromere. Here, the authors present cryo-EM and mutational studies that provide insights into the structure of the budding yeast centromeric nucleosome and how the centromere CBF3 protein complex guides its formation.

    • Ruifang Guan
    • , Tengfei Lian
    •  & Yawen Bai
  • Article
    | Open Access

    DNA methylation turnover is an essential epigenetic process during development. Here, the authors look at the changes in DNA methylation during the differentiation of post-mitotic human monocytes (MO), and find that EGR2 interacts with TET2 and is required for DNA demethylation at its binding sites; revealing EGR2 as an epigenetic pioneer factor in human MO.

    • Karina Mendes
    • , Sandra Schmidhofer
    •  & Michael Rehli
  • Article
    | Open Access

    ATAC-seq measures chromatin accessibility as a proxy for the activity of DNA regulatory regions across the genome. Here the authors present AtacWorks, a deep learning tool to denoise and identify accessible chromatin regions from low cell count, low-coverage, or low-quality ATAC-seq data.

    • Avantika Lal
    • , Zachary D. Chiang
    •  & Jason D. Buenrostro
  • Article
    | Open Access

    The methylation of Histone 3 at Lysine 36 (H3K36) has been implicated in the regulation of transcription and coupled processes such as mRNA splicing. Here the authors show that the histone methyltransferase SETD2 interacts with hnRNP L to mediate the crosstalk between the transcription and splicing machineries.

    • Saikat Bhattacharya
    • , Michaella J. Levy
    •  & Jerry L. Workman
  • Article
    | Open Access

    During differentiation, chromosome conformation is remodelled to support lineage-specific transcriptional programs. Here, the authors characterise chromosome conformational changes in B lymphocytes as they differentiate into plasma cells, and provide evidence that chromosome reconfiguration occurs prior to DNA replication and mitosis and guides gene expression that controls differentiation.

    • Wing Fuk Chan
    • , Hannah D. Coughlan
    •  & Rhys S. Allan
  • Article
    | Open Access

    Interaction between transcription factors and chromatin is fundamental for genome organization and regulation. Here, the authors use information theory to measure signatures of organized chromatin resulting from transcription factor-chromatin interactions, termed chromatin information enrichment, and find that variations in the information encoded in chromatin architecture reflects functional biological variation.

    • Ricardo D’Oliveira Albanus
    • , Yasuhiro Kyono
    •  & Stephen C. J. Parker