Epigenetics analysis

  • Article
    | Open Access

    The authors present epiScanpy: a computational framework for the analysis of single-cell epigenomic data, both ATAC-seq and DNA methylation data, with examples for clustering, cell type identification, trajectory learning and atlas integration - and show its performance in distinguishing cell types.

    • Anna Danese
    • , Maria L. Richter
    •  & Maria Colomé-Tatché
  • 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

    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

    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

    Extensive epigenetic reprogramming occurs during preimplantation embryo development. Here the authors develop a single cell multiomics sequencing technology that enables profiling of genome-wide chromatin accessibility, DNA methylation and RNA expression in the same individual cell and apply this method to study mouse preimplantation embryos.

    • Yang Wang
    • , Peng Yuan
    •  & Liying Yan
  • Article
    | Open Access

    Genetic elements that control inflammatory gene expression are not fully elucidated. Here the authors conduct a multi-species analysis of chromatin landscape and NF-κB binding in response to the proinflammatory cytokine TNFα, finding that conserved NF-κB bound regions are linked to enhancer activity and disease.

    • Azad Alizada
    • , Nadiya Khyzha
    •  & Michael D. Wilson
  • Article
    | Open Access

    Mast cells are critical effectors of allergic inflammation and protection against parasitic infections. Here the authors demonstrate that GATA2 promotes chromatin accessibility at the super-enhancers of mast cell identity genes and primes both typical and super-enhancers at genes that respond to antigenic stimulation.

    • Yapeng Li
    • , Junfeng Gao
    •  & Hua Huang
  • Article
    | Open Access

    The role of BRD4 and Mediator in regulating enhancer-promoter interactions is poorly understood. Here the authors find that treatment with BET inhibitors or pharmacological degradation of BRD4 disrupts transcription while having very little effect on enhancer-promoter interactions.

    • Nicholas T. Crump
    • , Erica Ballabio
    •  & Thomas A. Milne
  • Article
    | Open Access

    Histone acetylation is a ubiquitous hallmark of transcription. Here the authors provide evidence that the majority of histone acetylation is dependent on transcription, specifically due to the requirement of RNAPII for the recruitment and activity of histone acetyltransferases.

    • Benjamin J. E. Martin
    • , Julie Brind’Amour
    •  & LeAnn J. Howe
  • Article
    | Open Access

    Genomes are partitioned into topologically associating domains (TADs). Here the authors present single-nucleus Hi-C maps in Drosophila at 10 kb resolution, demonstrating the presence of chromatin compartments in individual nuclei, and partitioning of the genome into non-hierarchical TADs at the scale of 100 kb, which resembles population TAD profiles.

    • Sergey V. Ulianov
    • , Vlada V. Zakharova
    •  & Sergey V. Razin
  • Article
    | Open Access

    Current histone microarrays cannot be used to directly study the transient interactions of histone deacetylases (HDACs). Here, the authors show that hydroxamic acid-modified microarrays can capture HDACs, provide insights into their substrate specificity, and serve to develop peptide inhibitors.

    • Carlos Moreno-Yruela
    • , Michael Bæk
    •  & Christian A. Olsen
  • Article
    | Open Access

    Strong transgene suppression has been observed in Chlamydomonas reinhardtii, but the underlying mechanism is unknown. Here, the authors identify a sirtuin-type histone deacetylase that selectively acts on transgenic DNA to repress gene expression by assembling a repressive chromatin structure composed of deacetylated histones.

    • Juliane Neupert
    • , Sean D. Gallaher
    •  & Ralph Bock
  • Article
    | Open Access

    Hutchinson-Gilford progeria syndrome is a genetic disease where an aberrant form of Lamin A disrupts chromatin by interfering with lamina associated domains. Here, the authors present the SAMMY-seq, a method for genome-wide characterization of heterochromatin dynamics and detect early stage alterations of heterochromatin structure in progeria primary fibroblasts, accompained by Polycomb dysfunctions.

    • Endre Sebestyén
    • , Fabrizia Marullo
    •  & Chiara Lanzuolo
  • Article
    | Open Access

    Senescence is a state of stable proliferative arrest. Here, the authors perform Hi-C analysis on oncogenic RAS-induced senescence in human fibroblasts and characterize the changes in the 3D genome folding associated with the senescence-specific gene expression profile, which are mediated in part through cohesin redistribution on chromatin.

    • Ioana Olan
    • , Aled J. Parry
    •  & Masashi Narita
  • Article
    | Open Access

    PTSD has been associated with DNA methylation of specific loci in the genome, but studies have been limited by small sample sizes. Here, the authors perform a meta-analysis of DNA methylation data from 10 different cohorts and identify CpGs in AHRR that are associated with PTSD.

    • Alicia K. Smith
    • , Andrew Ratanatharathorn
    •  & Caroline M. Nievergelt
  • Article
    | Open Access

    Allele-specific measurements can reveal differences in DNA methylation between homologous alleles associated with changes in genetic sequence. Here, the authors develop a method for detecting allele specific methylation events within haplotypes of linked SNPs, compare it with existing methods, and show it identifies haplotypes for which the genetic variant carries significant information about the methylation state of the allele of origin.

    • J. Abante
    • , Y. Fang
    •  & J. Goutsias
  • Article
    | Open Access

    T cells are a major cell type involved in systemic lupus erythematosus (SLE). Here, the authors use promoter capture-C and ATAC-seq in human follicular T helper cells to identify SLE genes distant from GWAS loci (via 3D interaction) and validate the function of key regulatory elements and genes in vitro.

    • Chun Su
    • , Matthew E. Johnson
    •  & Andrew D. Wells
  • Article
    | Open Access

    Epstein-Barr virus (EBV) episomes tether to the host chromosome via EBNA1. Here, using circular chromosome conformation capture (4C), Kim et al. identify attachment sites and show that EBV episomes preferentially associate with transcriptionally silenced genes in Burkitt lymphoma cells.

    • Kyoung-Dong Kim
    • , Hideki Tanizawa
    •  & Paul M. Lieberman
  • Article
    | Open Access

    N6-methyladenosine (m6A) and N6,2′-O-dimethyladenosine (m6Am) are eukaryotic mRNA modifications. Here the authors develop m6A-Crosslinking-Exonuclease-sequencing to map quantitative methylome changes at single-base-resolution after individually knocking out each known methyltransferase or demethylase.

    • Casslynn W. Q. Koh
    • , Yeek Teck Goh
    •  & W. S. Sho Goh
  • Article
    | Open Access

    Although most are silenced, certain transposable elements (TEs) have been co-opted by the host. Here, the authors quantify the epigenomic status of TEs using data from the Roadmap Epigenomics Project, provide a systematic profile of TE activity across normal human tissues and development, finding that TEs encompass a quarter of the human regulatory epigenome, with 47% of TEs in regulatory states.

    • Erica C. Pehrsson
    • , Mayank N. K. Choudhary
    •  & Ting Wang
  • Article
    | Open Access

    Compared to bulk data, cell-type-specific DNA methylation data provide higher resolution of epigenetic variation. Here, the authors introduce Tensor Composition Analysis, a novel computational approach for learning cell-type-specific DNA methylation from tissue-level bulk data, and show its application in epigenome-wide association studies.

    • Elior Rahmani
    • , Regev Schweiger
    •  & Eran Halperin
  • Article
    | Open Access

    The SWI2/SNF2-Related 1 chromatin remodeling complex (SWR1-C) is important for gene regulation, but its composition remains largely uncharacterized in plants. Here, the authors report that methyl-CpG-binding domain 9 (MBD9) is a SWR1-C interacting protein required for histone H2A.Z deposition in Arabidopsis.

    • Magdalena E. Potok
    • , Yafei Wang
    •  & Steven E. Jacobsen
  • Article
    | Open Access

    Monoallelic expression of variant surface glycoprotein genes (VSGs) is essential for immune evasion by Trypanosoma brucei. Here, Faria et al. show that the VEX protein complex controls VSG allelic exclusion, and that CAF‐1 sustains inheritance of the VEX‐complex in association with the active VSG.

    • Joana Faria
    • , Lucy Glover
    •  & David Horn
  • Article
    | Open Access

    Master transcription factors dominantly direct cell fate and barriers ensuring their tissue specific silencing are not clearly defined. Here, the authors demonstrate that inefficient targeted transactivation of Sox1 in neural progenitor cells is surmountable through targeted promoter demethylation using dCas9-Tet1.

    • Valentin Baumann
    • , Maximilian Wiesbeck
    •  & Stefan H. Stricker
  • Article
    | Open Access

    Understanding gene regulation will require mapping specific chromain features in a small number of cells at high resolution. Here the authors describe CUT&Tag, which uses antibody-mediated tethering of Tn5 transposase to a chromatin protein to generate high resolution libraries.

    • Hatice S. Kaya-Okur
    • , Steven J. Wu
    •  & Steven Henikoff
  • Article
    | Open Access

    The spatial organization of the genome plays an important but unclearly defined role in gene regulation. Here, the authors integrate Hi-C, RNA-seq and ATAC-seq data to map cardiogenesis from pluripotent stem cells and describe an RBM20-dependent splicing factory assembling the TTN locus with other RBM20 targets.

    • Alessandro Bertero
    • , Paul A. Fields
    •  & Charles E. Murry
  • Article
    | Open Access

    The inactive X chromosome (Xi) is a model for establishment and maintenance of repressed chromatin and the function of polycomb repressive complexes. Here the authors show that Xi transiently relocates from the nuclear periphery during replication in a CIZ1-dependent manner, which plays a role in maintaining PRC-mediated repressed chromatin.

    • Emma R. Stewart
    • , Robert M. L. Turner
    •  & Dawn Coverley
  • Article
    | Open Access

    Our knowledge of DNA methylation systems in prokaryotes is mostly limited to those of culturable microbes. Here, Hiraoka et al. analyse DNA methylation patterns in metagenomic data from a microbial community, revealing new methylated motifs and experimentally validating the methyltransferases’ specificities.

    • Satoshi Hiraoka
    • , Yusuke Okazaki
    •  & Wataru Iwasaki
  • Article
    | Open Access

    Chromatin conformation studies are limited by the large amounts of starting material required to perform current protocols. Here the authors present Low-C, a Hi-C method for low amounts of input material and produce Low-C maps from primary B-cells of a diffuse large B-cell lymphoma patient, demonstrating the suitability of Low-C to analyse rare cell populations.

    • Noelia Díaz
    • , Kai Kruse
    •  & Juan M. Vaquerizas
  • Article
    | Open Access

    Cellular heterogeneity in cancer is complex and difficult to study. Here, the authors introduce Protein-indexed Assay of Transposase Accessible Chromatin (Pi-ATAC), which combines single cell chromatin and proteomic profiling to provide deep insight into the tumor microenvironment, and reveal the role of hypoxia in shaping the regulome of a subset of breast cancer cells in vivo.

    • Xingqi Chen
    • , Ulrike M. Litzenburger
    •  & Howard Y. Chang
  • Article
    | Open Access

    Mitosis poses a challenge for transcriptional programs, as it is thought that several proteins lose binding on condensed chromosomes. Here, the authors analyze the chromatin-bound proteome through the cell cycle, revealing retention of most transcription factors and preservation of the regulatory landscape.

    • Paul Adrian Ginno
    • , Lukas Burger
    •  & Dirk Schübeler
  • Article
    | Open Access

    Single-cell chromatin accessibility is a promising means to identify regulatory programs in mixtures of cells. Here the authors describe µ-ATAC-seq, a low-cost method that can generate thousands of accessibility profiles per day.

    • Anja Mezger
    • , Sandy Klemm
    •  & William Greenleaf
  • Article
    | Open Access

    Incorporation of histone H3 variant H3.3 into chromatin regulates transcription. Here the authors find that H3.3 sub-variant H3mm7 is required for skeletal muscle regeneration and that H3mm7 nucleosomes are unstable and exhibit higher mobility, with H3mm7 promoting open chromatin around promoters.

    • Akihito Harada
    • , Kazumitsu Maehara
    •  & Yasuyuki Ohkawa
  • Article
    | Open Access

    The limited size of some neuronal types and their entangled environment renders it difficult to study their transcription regulation. Here the authors present a comparative analysis of histone modifications and transcription in dopaminergic and serotonergic neurons and embryonic neural progenitors.

    • Erik Södersten
    • , Konstantinos Toskas
    •  & Johan Holmberg
  • Article
    | Open Access

    Relationships between DNA methylation and transcription, and methylation and DNA accessibility can be probed but interrogating all three in the same single cells has not been possible. Here, the authors report the first single-cell method for parallel chromatin accessibility, DNA methylation and transcriptome profiling.

    • Stephen J. Clark
    • , Ricard Argelaguet
    •  & Wolf Reik
  • Article
    | Open Access

    SETDB1 is a histone methyltransferase that generates H3K9me3 marks in euchromatic regions. Here the authors show that the triple Tudor domain (3TD) of SETDB1 binds histone H3 tails containing K14 acetylation combined with K9 methylation, and that the K9me–K14ac modification defines a novel chromatin state enriched at SETDB1 binding sites.

    • Renata Z. Jurkowska
    • , Su Qin
    •  & Albert Jeltsch