Chromatin, Epigenetics, Genomics & Functional Genomics
- Akirin specifies NF‐κB selectivity of Drosophila innate immune response via chromatin remodeling
- François Bonnay1,†,
- Xuan‐Hung Nguyen1,†,
- Eva Cohen‐Berros1,
- Laurent Troxler1,
- Eric Batsche2,
- Jacques Camonis3,
- Osamu Takeuchi4,
- Jean‐Marc Reichhart1 and
- Nicolas Matt*,1
- 1UPR9022 du CNRS, Institut de Biologie Moléculaire et Cellulaire Université de Strasbourg, Strasbourg Cedex, France
- 2Département de Biologie du Développement, Institut Pasteur, CNRS URA2578, Unité de Régulation Epigénétique, Paris, France
- 3Institut Curie INSERM U‐528, Paris Cedex, France
- 4Laboratory of Infection and Prevention, Institute for Virus Research Kyoto University CREST, JST, Sakyo‐ku, Kyoto, Japan
- ↵*Corresponding author. Tel: +33 388 417 089; Fax: +33 388 606 922; E‐mail: n.matt{at}unistra.fr
-
↵† These authors contributed equally to this work
The nuclear factor Akirin orchestrates NF‐κB transcriptional selectivity through the recruitment of the Osa‐containing‐SWI/SNF Brahma complex (BAP), by activating a subset of NF‐κB effector genes.
Synopsis
The nuclear factor Akirin orchestrates NF‐κB transcriptional selectivity through the recruitment of the Osa‐containing‐SWI/SNF Brahma complex (BAP), by activating a subset of NF‐κB effector genes.
In the Drosophila innate immune response, Akirin is required for NF‐κB selectivity.
Akirin interacts with the SWI/SNF Bap60 subunit upon immune challenge.
Akirin promotes SWI/SNF (BAP)‐dependent activation of a subset of immuno‐induced genes.
Relish, Akirin and Bap60 are recruited on a subset of NF‐κB‐dependent promoters.
SWI/SNF‐like (BAP) complex is required for fly defense against Gram‐negative bacteria.
The EMBO Journal (2014) 33: 2349–2362
- Received March 10, 2014.
- Revision received August 7, 2014.
- Accepted August 8, 2014.
- © 2014 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.
- Taming the young and restless—epigenetic gene regulation in pancreas and beta‐cell precursors
The in vivo assessment of epigenetic changes during mouse pancreatic beta‐cell differentiation reveals surprising differences to directed, in vitro differentiation of human embryonic stem cells. New findings reported in this issue of The EMBO Journal further identify Ezh2 as a critical determinant of endocrine progenitor number and could instruct improved protocols for stem cell‐based therapies.
See also: CR Xu et al (October 2014)
A new study reports genome‐wide occupancy maps of H3K27me3 during pancreatic progenitor differentiation. The functional perturbation of Ezh2 increases endocrine progenitor fate and could thus inform therapeutically relevant differentiation protocols.
- © 2014 The Authors
- Dynamics of genomic H3K27me3 domains and role of EZH2 during pancreatic endocrine specification
- Cheng‐Ran Xu1,2,
- Lin‐Chen Li2,
- Greg Donahue1,
- Lei Ying3,
- Yu‐Wei Zhang2,
- Paul Gadue3 and
- Kenneth S Zaret*,1
- 1Institute for Regenerative Medicine, Epigenetics Program, Department of Cell and Developmental Biology, Perelman School of Medicine University of Pennsylvania, Philadelphia, PA, USA
- 2Ministry of Education Key Laboratory of Cell Proliferation, College of Life Sciences Peking‐Tsinghua Center for Life Sciences Peking University, Beijing, China
- 3Department of Pathology and Laboratory Medicine, Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA, USA
- ↵*Corresponding author. Tel: +1 215 573 5813; E‐mail: zaret{at}upenn.edu
The in vivo analysis of Ezh2‐dependent H3K27me3‐dynamics during pancreatic endocrine specification could instruct optimized ES cell differentiation for future therapeutic application.
Synopsis
The in vivo analysis of Ezh2‐dependent H3K27me3‐dynamics during pancreatic endocrine specification could instruct optimized ES cell differentiation for future therapeutic application.
During pancreatic endocrine development in embryos, genes that gain H3K27me3 typically are involved in cell biology and morphogenesis, whereas genes that lose H3K27me3 are typically involved in developmental gene regulation.
The gain in H3K27me3 domains observed in pancreas development in embryos differs from the decline in such domains reported for ES cell differentiation to pancreas progenitors in vitro.
Genetic diminution of Ezh2 at the pancreas progenitor stage in embryos enhances the subsequent production of endocrine progenitors and beta cells.
Inhibition of EZH2 at the endocrine progenitor induction stage in differentiating human ES cells increases the production of beta‐like cells in vitro.
The EMBO Journal (2014) 33: 2157–2170
- Received April 6, 2014.
- Revision received July 11, 2014.
- Accepted July 16, 2014.
- © 2014 The Authors
- Akirin2 is critical for inducing inflammatory genes by bridging IκB‐ζ and the SWI/SNF complex
- Sarang Tartey1,2,3,4,
- Kazufumi Matsushita5,
- Alexis Vandenbon6,
- Daisuke Ori1,2,
- Tomoko Imamura1,2,
- Takashi Mino1,2,
- Daron M Standley6,
- Jules A Hoffmann7,
- Jean‐Marc Reichhart7,
- Shizuo Akira3,4 and
- Osamu Takeuchi*,1,2,3
- 1Laboratory of Infection and Prevention Institute for Virus Research Kyoto University, Sakyo‐ku Kyoto, Japan
- 2CREST JST, Sakyo‐ku Kyoto, Japan
- 3Laboratory of Host Defense WPI Immunology Frontier Research Center (IFReC), Osaka University Suita, Osaka, Japan
- 4Research Institute for Microbial Diseases Osaka University, Suita Osaka, Japan
- 5Laboratory of Allergic Diseases Institute for Advanced Medical Sciences Hyogo College of Medicine, Suita Osaka, Japan
- 6Laboratory of Systems Immunology WPI Immunology Frontier Research Center (IFReC), Nishinomiya Hyogo, Japan
- 7IBMC UPR 9022 CNRS, Strasbourg Cedex, France
- ↵*Corresponding author. Tel: +81 75 751 4024; Fax: +81 75 761 5766; E‐mail: otake{at}virus.kyoto-u.ac.jp
By recruiting SWI/SNF chromatin remodellers to NF‐κB, the conserved nuclear protein Akirin2 stimulates pro‐inflammatory gene promoters in mouse macrophages during innate immune responses to viral or bacterial infection.
Synopsis
By recruiting SWI/SNF chromatin remodellers to NF‐κB, the conserved nuclear protein Akirin2 stimulates pro‐inflammatory gene promoters in mouse macrophages during innate immune responses to viral or bacterial infection.
Akirin2 is critical for Toll‐like receptor‐ and RIG‐I‐like receptor‐induced cytokine production in mouse macrophages
Akirin2 is critical for the responses to Listeria monocytogenes infection in living mice
Akirin2 enables LPS‐induced chromatin remodelling in a SWI/SNF‐dependent manner
The NF‐κBp50‐IκB‐ζ‐Akirin2 cascade is critical for the recruitment of Brg1, the SWI/SNF core catalytic subunit, to the Il6 promoter.
The EMBO Journal (2014) 33: 2332–2348
- Received March 10, 2014.
- Revision received July 5, 2014.
- Accepted July 9, 2014.
- © 2014 The Authors
- Epigenetic memory in plants
- ↵*
Corresponding author. Tel: +44 1223 761159; E‐mail: mayumi.iwasaki{at}slcu.cam.ac.uk
Corresponding author. Tel: +44 1223 761159; E‐mail: jerzy.paszkowski{at}slcu.cam.ac.uk
Review series on Molecular Memory: epigenetic modifications shape development, adaptation and cellular memory in plants.
The EMBO Journal (2014) 33: 1987–1998
- Received May 5, 2014.
- Revision received June 6, 2014.
- Accepted June 17, 2014.
- © 2014 The Authors
- ↵*
Corresponding author. Tel: +44 1223 761159; E‐mail: mayumi.iwasaki{at}slcu.cam.ac.uk
- Post‐transcriptional gene expression control by NANOS is up‐regulated and functionally important in pRb‐deficient cells
- Wayne O Miles1,
- Michael Korenjak1,
- Lyra M Griffiths2,
- Michael A Dyer2,
- Paolo Provero3,4 and
- Nicholas J Dyson*,1
- 1Massachusetts General Hospital Cancer Center and Harvard Medical School Laboratory of Molecular Oncology, Charlestown, MA, USA
- 2Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA
- 3Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy
- 4Center for Translational Genomics and Bioinformatics, San Raffaele Scientific Institute, Milan, Italy
- ↵*Corresponding author. Tel: +1 617 726 7800; Fax: +1 617 726 7808; E‐mail: dyson{at}helix.mgh.harvard.edu
Post‐transcriptional gene expression control by NANOS is up‐regulated and functionally important in pRb‐deficient cells. Interplay of transcriptional and posttranscriptional gene regulation explains how cells with mutations in the retinoblastoma tumor suppressor can contribute relatively normally to tissues in mice and flies.
Synopsis
Despite of lost control over E2F transcriptional programs, cells with pRb mutations can contribute relatively normally to tissues in mice and flies. Complete gene expression deregulation is prevented by the post‐transcriptional regulator NANOS, which is normally repressed by pRb but upregulated in its absence.
pRb activity increases the binding of repressor complexes such as dREAM to the NANOS promoter.
Elevated NANOS levels promote proliferation and survival of pRb‐deficient cells, as well as homeostasis of RBF1‐depleted tissues.
NANOS upregulation reduces cellular stress associated with pRb inactivation in part by post‐transcriptionally silencing stress‐response genes, including MAP kinases that act upstream of p53.
Repression of NANOS expression by E2F/pRb is conserved from flies to humans.
The EMBO Journal (2014) 33: 2201–2215
- Received January 28, 2014.
- Revision received July 11, 2014.
- Accepted July 15, 2014.
- © 2014 The Authors
- Sox2, a marker for stem‐like tumor cells in skin squamous cell carcinoma and hedgehog subgroup medulloblastoma
- 1Division of Pediatric Hematology‐Oncology, Duke University Medical Center, Durham, NC, USA
- 2Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA
- 3Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- 4Alvord Brain Tumor Center, University of Washington, Seattle, WA, USA
Heterogeneity within tumors is becoming increasingly recognized as an important cause of treatment failure in cancer. Two recent studies use fate‐mapping and limiting dilution transplantation assays to identify SRY (sex determining region Y)‐box 2 (Sox2) as cancer stem‐cell marker and driver of cancer stemness.
See also: RJ Vanner et al (July 2014),
S Boumahdi et al (July 2014) and
M Kool et al (March 2014)
The identification of Sox2 as cancer stem‐cell marker and driver of cancer stemness in distinct tumor types suggests that each tumor resembles the hierarchical organization of the tissue from which it arises.
- © 2014 The Authors
- Insulators recruit histone methyltransferase dMes4 to regulate chromatin of flanking genes
- Priscillia Lhoumaud1,†,
- Magali Hennion1,†,
- Adrien Gamot1,†,
- Suresh Cuddapah27,
- Sophie Queille1,
- Jun Liang1,
- Gael Micas1,
- Pauline Morillon1,
- Serge Urbach3,
- Olivier Bouchez4,
- Dany Severac5,
- Eldon Emberly6,
- Keji Zhao2 and
- Olivier Cuvier*,1
- 1Laboratoire de Biologie Moléculaire Eucaryote (LBME), CNRS Université de Toulouse (UPS), Toulouse, France
- 2Systems Biology Center, National Heart, Lung and Blood Institute National Institutes of Health (NIH), Bethesda, MD, USA
- 3Mass‐Spectrometry Facility, Institut de Génomique Fonctionnelle, Montpellier, France
- 4UMR444‐Laboratoire de Génétique Cellulaire & GeT‐PlaGe, INRA Genotoul, Auzeville, Toulouse, France
- 5MGX‐Montpellier GenomiX, Institut de Génomique Fonctionnelle, Montpellier, France
- 6Physics Department, Simon Fraser University (SFU), Burnaby, BC, Canada
- 7 Department of Environmental Medicine, New York University School of Medicine, Tuxedo, NY, USA
- ↵*Corresponding author. Tel: +33 561 335956; E‐mail: cuvier{at}ibcg.biotoul.fr
-
↵† These authors contributed equally to the work
Insulator‐binding proteins (IBPs) separate chromatin domains. The IBP dCTCF/Beaf32 and the H3K36 histone methyltransferase NSD/dMes‐4 co‐regulate the nucleosome dynamics, chromatin accessibility, and gene expression of insulator‐flanked genes.
Synopsis
Insulator‐binding proteins (IBPs) separate chromatin domains. The IBP dCTCF/Beaf32 and the H3K36 histone methyltransferase NSD/dMes‐4 co‐regulate nucleosome dynamics, chromatin accessibility, and expression of insulator‐flanked genes.
Insulator proteins interact with H3K36 histone methyltransferase NSD/dMes‐4.
Expression data show that dMes4 acts as a cofactor of IBPs.
H3K36me2/3 regulate transcription‐coupled nucleosome dynamics and RNA splicing.
IBPs/dMes‐4 regulate H3K27me3 deposition for hundreds of genes.
The EMBO Journal (2014) 33: 1599–1613
- Received June 11, 2013.
- Revision received February 7, 2014.
- Accepted April 1, 2014.
- © 2014 The Authors
- Chromatin regulates DNA torsional energy via topoisomerase II‐mediated relaxation of positive supercoils
- 1Instituto de Biología Molecular de Barcelona (IBMB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, Spain
- ↵*Corresponding author. Tel: +34 9340 20117; Fax: +34 9340 34979; E‐mail: joaquim.roca{at}ibmb.csic.es
Differential (+) and (−) torsional stress relaxation by topoisomerases I and II contributes to the overall negative supercoiling status of native chromatin, which may facilitate transactions such as DNA unwinding.
Synopsis
Comparative in vivo analyses show that twin domains of positive (+) and negative (−) DNA torsional stress, which simultaneously arise during DNA transcription, are not relaxed at the same rate in vivo. These findings suggest that the overall negative supercoiling status of native chromatin stems from differential relaxation activities of topoisomerases I and II.
Chromatin delays the relaxation of both positive and negative DNA torsional stress by topoisomerase I.
Chromatin favors quick relaxation of positive DNA supercoils by topoisomerase II.
Unbalanced relaxation of positive supercoils may facilitate DNA unwinding in eukaryotic chromatin.
The EMBO Journal (2014) 33: 1492–1501
- Received January 31, 2014.
- Revision received April 11, 2014.
- Accepted April 29, 2014.
- © 2014 The Authors
- Eaf5/7/3 form a functionally independent NuA4 submodule linked to RNA polymerase II‐coupled nucleosome recycling
- Dorine Rossetto1,
- Myriam Cramet1,†,
- Alice Y Wang24†,
- Anne‐Lise Steunou1,†,
- Nicolas Lacoste13,
- Julia M Schulze25,
- Valérie Côté1,
- Julie Monnet‐Saksouk1,
- Sandra Piquet1,
- Amine Nourani1,
- Michael S Kobor2 and
- Jacques Côté*,1
- 1St‐Patrick Research Group in Basic Oncology, Laval University Cancer Research Center Centre de Recherche du CHU de Québec‐Axe Oncologie Hôtel‐Dieu de Québec, Quebec City, QC, Canada
- 2Center for Molecular Medicine and Therapeutics, Child and Family Research Institute, Vancouver, BC, Canada
- 3 Institut Curie/CNRS, UMR3664, Paris, France
- 4 Hotchkiss Brain Institute Faculty of Medicine University of Calgary, Calgary AB, Canada
- 5 Department of Medical and Applied Genetics University of Tübingen, Tübingen, Germany
- ↵*Corresponding author. Tel: +1 418 525 4444, ext. 15545; E‐mail: Jacques.Cote{at}crhdq.ulaval.ca
-
↵† These authors contributed equally to this work
Dissection of the essential multisubunit NuA4 acetyltransferase reveals a trimeric subcomplex that interacts with elongating RNA polymerase II and functions independently to control transcription‐coupled histone exchange.
Synopsis
The multisubunit NuA4 complex is an essential gene regulatory acetyltransferase in yeast. Dissection of its subunits reveals a trimeric submodule independently associating with gene coding regions, which may act as a histone chaperone during RNA polymerase II transcriptional elongation.
Eaf5/7/3 forms a submodule within the NuA4 acetyltransferase complex and also functions as an independent native trimer.
High‐resolution genome‐wide analysis reveals NuA4 binding to promoters and coding regions of actively transcribed genes.
The Eaf5/7/3 trimer independently associates with the coding region of transcriptionally active genes and affects RNA polymerase II processivity.
Eaf5/7/3 interacts with phosphorylated, elongating RNA polymerase II and H3K36me3‐containing nucleosomes.
Eaf5/7/3 cooperates with FACT to promote transcription‐coupled nucleosomes disruption, as well as their refolding behind the polymerase to suppress histone exchange.
The EMBO Journal (2014) 33: 1397–1415
- Received July 29, 2013.
- Revision received April 14, 2014.
- Accepted April 17, 2014.
- © 2014 The Authors
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