Chromatin, Epigenetics, Genomics & Functional Genomics
- SIRT7 clears the way for DNA repair
Histone modification by reversible lysine acetylation is a key regulatory mechanism in chromatin and nuclear signaling, whose deregulation is linked to aging, cancer, and other diseases. New work by Vazquez et al (2016) uncovers a role for the sirtuin family deacetylase SIRT7, which controls epigenetic maintenance of oncogenic gene expression programs, mitochondrial homeostasis, and ribosome biogenesis, in promoting genomic stability and DNA repair via site‐specific deacetylation of a damage‐associated histone mark, H3K18Ac.
See also: BN Vazquez et al (July 2016)
New mouse model uncovers histone H3 K18 deacetylation by a nuclear sirtuin as an important modulator of genome stability and repair pathway choice.
- © 2016 The Authors
- Transcription rate and transcript length drive formation of chromosomal interaction domain boundaries
- 1Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA
- 2Department of Molecular Microbiology, John Innes Centre, Norwich, UK
- 3Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, USA
- ↵*Corresponding author. Tel: +1 617 324 0418; E‐mail: laub{at}mit.edu
Chromosome conformation capture in conjunction with deep sequencing (Hi‐C) and fluorescence microscopy identify mechanisms for topological domain in Caulobacter crescentus chromosomes.
Synopsis
Chromosomes universally consist of multiple topological interaction domains. Chromosome conformation capture in conjunction with deep sequencing (Hi‐C) and fluorescence microscopy identify mechanisms for topological domain in Caulobacter crescentus chromosomes.
The boundaries between chromosomal interaction domains seen in Hi‐C maps of Caulobacter are frequently associated with long, highly expressed genes.
Domain boundaries are typically associated with highly expressed genes longer than ˜2 kb.
Translating ribosomes do not contribute to domain boundary formation.
Transcription rate and transcript length contribute to an inhibition of supercoil diffusion, but this is not a primary factor in creating Hi‐C boundaries.
Long transcripts locally decompact DNA, which separates the flanking loci and creates the boundaries visible by Hi‐C.
The EMBO Journal (2016) 35: 1582–1595
- Received November 25, 2015.
- Revision received May 16, 2016.
- Accepted May 20, 2016.
- © 2016 The Authors
- Continual removal of H3K9 promoter methylation by Jmjd2 demethylases is vital for ESC self‐renewal and early development
- Marianne Terndrup Pedersen1,2,†,
- Susanne Marije Kooistra1,2,5,†,
- Aliaksandra Radzisheuskaya1,2,
- Anne Laugesen1,2,3,
- Jens Vilstrup Johansen1,
- Daniel Geoffrey Hayward4,
- Jakob Nilsson4,
- Karl Agger1,2 and
- Kristian Helin*,1,2,3
- 1Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark
- 2Centre for Epigenetics, University of Copenhagen, Copenhagen, Denmark
- 3The Danish Stem Cell Center (Danstem), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- 4The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- 5Department of Neuroscience, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
- ↵*Corresponding author. Tel: +45 3532 5666; E‐mail: kristian.helin{at}bric.ku.dk
↵† These authors contributed equally to this work
A set of newly generated conditional deletion models shows that histone demethylases Jmjd2a and Jmjd2c are highly redundant and that their regulation of H3K9 promoter methylation is vital for ESC self‐renewal.
Synopsis
A set of newly generated conditional deletion models shows that histone demethylases Jmjd2a and Jmjd2c are highly redundant and that their regulation of H3K9 promoter methylation is vital for ESC self‐renewal.
Knockout of Jmjd2 demethylases reveals redundant and essential functions of Jmjd2a and Jmjd2c in early embryogenesis.
Loss of both Jmjd2a and Jmjd2c impairs ESC self‐renewal in 2i as well as serum culture.
Jmjd2a and Jmjd2c both localize to H3K4me3‐marked TSSs and continuously prevent accumulation of H3K9me3 and H3K36me3.
In the absence of Jmjd2a/c catalytic activity, increased H3K9me3 levels at TSSs compromise the expression of genes required for ESC maintenance.
The EMBO Journal (2016) 35: 1550–1564
- Received October 20, 2015.
- Revision received April 15, 2016.
- Accepted May 6, 2016.
- © 2016 The Authors
- Nucleosome eviction in mitosis assists condensin loading and chromosome condensation
- Esther Toselli‐Mollereau1,†,
- Xavier Robellet1,†,
- Lydia Fauque1,†,
- Sébastien Lemaire1,
- Christoph Schiklenk2,
- Carlo Klein2,
- Clémence Hocquet1,
- Pénélope Legros1,
- Lia N'Guyen1,
- Léo Mouillard1,
- Emilie Chautard1,
- Didier Auboeuf1,
- Christian H Haering2 and
- Pascal Bernard*,1
- 1Laboratory of Biology and Modelling of the Cell, Univ Lyon, ENS de Lyon, Univ Claude Bernard, CNRS UMR 5239, INSERM U1210, Lyon, France
- 2Cell Biology and Biophysics Unit, EMBL, Heidelberg, Germany
- ↵*Corresponding author. Tel: +33 672 728 197; E‐mail: pascal.bernard{at}ens-lyon.fr
↵† These authors contributed equally to this work
Fission yeast condensin accumulates at nucleosome‐depleted regions in the vicinity of highly expressed genes, implying the nucleosomes hinder condensin binding.
Synopsis
Fission yeast condensin accumulates at nucleosome‐depleted regions in the vicinity of highly expressed genes. Nucleosomes hinder condensin localization, and their eviction coupled with transcription seems a key feature of condensin‐binding sites.
Condensin accumulates at nucleosome‐depleted regions during mitosis in fission yeast.
Nucleosome eviction by transcriptional co‐activators such as Gcn5, Mst2 and RSC is necessary for condensin binding and proper chromosome condensation.
Nucleosome constitutes an obstacle for condensin localization.
The presence of free, non‐nucleosomal DNA might be an important feature of condensin‐binding sites in eukaryotes.
The EMBO Journal (2016) 35: 1565–1581
- Received August 15, 2015.
- Revision received May 3, 2016.
- Accepted May 5, 2016.
- © 2016 The Authors
- Structural evidence for Nap1‐dependent H2A–H2B deposition and nucleosome assembly
- Carmen Aguilar‐Gurrieri1,2,
- Amédé Larabi1,2,
- Vinesh Vinayachandran3,
- Nisha A Patel4,
- Kuangyu Yen5,
- Rohit Reja3,
- Ima‐O Ebong4,
- Guy Schoehn2,6,7,8,
- Carol V Robinson4,
- B Franklin Pugh3 and
- Daniel Panne*,1,2
- 1European Molecular Biology Laboratory, Grenoble, France
- 2Unit for Virus Host–Cell Interactions, Univ. Grenoble Alpes–EMBL–CNRS, Grenoble, France
- 3Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, USA
- 4Department of Chemistry, University of Oxford, Oxford, UK
- 5Department of Cell Biology, Southern Medical University, Guangzhou, China
- 6Université Grenoble–Alpes, Grenoble, France
- 7Centre National de la Recherche Scientifique (CNRS) IBS, Grenoble, France
- 8CEA, IBS, Grenoble, France
- ↵*Corresponding author. Tel: +33 476207925; E‐mail: panne{at}embl.fr
A co‐crystal structure defines the stoichiometry of H2A–H2B binding to the Nap1 histone chaperone, and shows that higher‐order oligomerization is needed for proper histone incorporation into nucleosomes.
Synopsis
A co‐crystal structure defines the stoichiometry of H2A–H2B binding to the Nap1 histone chaperone and shows that higher‐order oligomerization is needed for proper histone incorporation into nucleosomes.
Crystal structure of the Nap1–H2A–H2B complex at 6.7 Å resolution.
A Nap1 dimer binds a single H2A–H2B dimer.
Nap1 prevents non‐specific DNA binding of H2A–H2B and is required for H2A–H2B deposition and nucleosome assembly in vivo.
Oligomerization of the Nap1–H2A–H2B complex is important for the chaperone function of Nap1.
The EMBO Journal (2016) 35: 1465–1482
- Received February 12, 2016.
- Revision received April 9, 2016.
- Accepted April 21, 2016.
- © 2016 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- SIRT7 promotes genome integrity and modulates non‐homologous end joining DNA repair
- Berta N Vazquez1,
- Joshua K Thackray1,
- Nicolas G Simonet2,
- Noriko Kane‐Goldsmith1,
- Paloma Martinez‐Redondo2,
- Trang Nguyen1,
- Samuel Bunting3,
- Alejandro Vaquero2,
- Jay A Tischfield1 and
- Lourdes Serrano*,1
- 1Department of Genetics, Human Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ, USA
- 2Chromatin Biology Laboratory, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
- 3Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ, USA
- ↵*Corresponding author. Tel: +1 848 445 9577; E‐mail: serrano{at}biology.rutgers.edu
Increased replication stress and impaired DNA damage response in SIRT7‐deficient cells are linked to developmental defects and accelerated again in SIRT7 KO mice.
Synopsis
Sirtuins are deacetylase enzymes implicated in genome stability and life span regulation. Here, the roles of SIRT7 in genome function are studied by characterization of SirT7−/− mice.
Loss of SIRT7 results in reduced embryonic viability, accelerated aging, and genomic instability.
SIRT7 is recruited to sites of DNA damage in a PARP‐dependent manner.
SIRT7 participates in the DNA damage response by promoting NHEJ DNA repair.
SIRT7‐dependent H3K18 deacetylation is important for efficient 53BP1 recruitment at DNA damage sites.
SIRT7‐deficient cells show increased levels of replication stress, which may underlie progeroid phenotypes.
The EMBO Journal (2016) 35: 1488–1503
- Received November 16, 2015.
- Revision received March 21, 2016.
- Accepted April 27, 2016.
- © 2016 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Histone H3.3 promotes IgV gene diversification by enhancing formation of AID‐accessible single‐stranded DNA
- ↵*Corresponding author. Tel: +44 1223 267099; E‐mail: jes{at}mrc-lmb.cam.ac.uk
↵† These authors contributed equally to this work
The presence of variant histone H3.3 in immunoglobulin V genes promotes the exposure of ssDNA during transcription, thus enabling efficient AID‐mediated antibody diversification.
Synopsis
Cytidine‐to‐uracil conversion by activation‐induced deaminase (AID) requires single‐stranded DNA regions in immunoglobulin V genes. The presence of variant histone H3.3 promotes ssDNA exposure during transcription, thus enabling efficient AID‐mediated antibody diversification.
DT40 chicken B cells lacking variant histone H3.3 exhibit defective AID‐mediated antibody diversification.
This defect is not linked to altered Ig gene transcription or RNA polymerase II elongation kinetics.
H3.3 promotes exposure of single‐stranded DNA in the IgV region, thereby creating an effective AID substrate.
Formation of R‐loops in the IgV genes is secondary to ssDNA exposure and not necessary for AID access.
The EMBO Journal (2016) 35: 1452–1464
- Received January 25, 2016.
- Revision received April 7, 2016.
- Accepted April 25, 2016.
- © 2016 MRC Laboratory of Molecular Biology. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Parental epigenetic asymmetry of PRC2‐mediated histone modifications in the Arabidopsis endosperm
- 1Department of Plant Biology, Uppsala BioCenter, Swedish University of Agricultural Sciences and Linnean Center of Plant Biology, Uppsala, Sweden
- ↵*Corresponding author. Tel: +46 18 67 3313; E‐mail: claudia.kohler{at}slu.se
Genomewide mapping of the epigenetic state in early plant endosperm links polycomb to the maintenance of parental imprinting and explains how DNA hypomethylation of the maternal genome is maintained after fertilization.
Synopsis
Genomewide mapping of the epigenetic state in early plant endosperm links Polycomb to the maintenance of parental imprinting and explains how DNA hypomethylation of the maternal genome is maintained after fertilization.
The polycomb‐mediated histone mark H3K27me3 has a parent‐of‐origin‐specific distribution in the endosperm and determines the imprinting status of paternally expressed imprinted genes.
The early endosperm is largely devoid of CHH methylation, providing an explanation of how hypomethylation of the maternal genome is maintained after fertilization.
Paternal‐specific H3K27me3 is localized at pericentromeric regions and has no major impact on the regulation of maternally expressed imprinted genes.
The EMBO Journal (2016) 35: 1298–1311
- Received November 20, 2015.
- Revision received March 14, 2016.
- Accepted March 17, 2016.
- © 2016 The Authors
- Nucleosomal arrays self‐assemble into supramolecular globular structures lacking 30‐nm fibers
- Kazuhiro Maeshima*,1,2,†,
- Ryan Rogge3,†,
- Sachiko Tamura1,
- Yasumasa Joti2,4,
- Takaaki Hikima2,
- Heather Szerlong3,
- Christine Krause3,
- Jake Herman3,
- Erik Seidel3,
- Jennifer DeLuca3,
- Tetsuya Ishikawa2 and
- Jeffrey C Hansen*,3
- 1Biological Macromolecules Laboratory, Structural Biology Center, National Institute of Genetics and Department of Genetics, Sokendai (Graduate University for Advanced Studies), Mishima, Japan
- 2RIKEN SPring‐8 Center, Sayo‐cho, Sayo‐gun, Japan
- 3Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO, USA
- 4XFEL Utilization Division, Japan Synchrotron Radiation Research Institute (JASRI), Sayo‐gun, Japan
- ↵*
Corresponding author. Tel: +81 55 981 6864; E‐mail: kmaeshim{at}nig.ac.jp
Corresponding author. Tel: +1 970 491 5440; E‐mail: jeffrey.c.hansen{at}colostate.edu
↵† These authors contributed equally to this work
An in vitro system for chromatin packaging shows that short array of nucleosomes has the intrinsic ability to self‐assemble into large chromatin globules devoid of folded 30‐nm fibers.
Synopsis
An in vitro system for chromatin packaging shows that short array of nucleosomes has the intrinsic ability to self‐assemble into large chromatin globules devoid of folded 30‐nm fibers.
Nucleosomal arrays self‐associate into large globular structures in a Mg2+‐dependent manner.
The globular structures range in size from ˜50 to 1,000 nm in diameter, sediment between ˜5,000–350,000 S, and contain ˜1–400 Mb DNA/structure.
The packaged nucleosomal arrays adopt extended 10‐nm fibers, not folded 30‐nm fibers.
Nucleosomal and H1‐arrays can fold into 30‐nm fibers in vitro, but only under very specific ionic conditions.
Both linker DNA and attractive nucleosome–nucleosome interactions contribute to the formation and stability of the globular structures.
The EMBO Journal (2016) 35: 1115–1132
- Received August 1, 2015.
- Revision received February 2, 2016.
- Accepted March 8, 2016.
- © 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license
This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs 4.0 License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
- The cis‐regulatory switchboard of pancreatic ductal cancer
- 1Section of Epigenomics and Disease, Department of Medicine, Imperial College London, London, UK
- 2Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Institut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Barcelona, Spain
- 3Epithelial Carcinogenesis Group, Cancer Cell Biology Programme, Spanish National Cancer Research Center‐CNIO, Madrid, Spain
- 4Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most devastating human diseases. There is consequently a pressing need to understand its molecular underpinnings, which should enable new preventive and therapeutic strategies. A new study in The EMBO Journal (Diaferia et al, 2016) maps the transcriptome and epigenetic landscape associated with distinct PDAC grades and identifies cis‐ and trans‐regulatory elements in tumour progression.
See also: GR Diaferia et al (March 2016)
A new genomewide study identifies cis‐ and trans‐regulatory elements in pancreatic ductal carcinoma, thus shedding light on the mechanisms underlying tumour progression.
- © 2016 The Authors
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