Chromatin, Epigenetics, Genomics & Functional Genomics
- 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
- Inducible chromatin priming is associated with the establishment of immunological memory in T cells
- Sarah L Bevington1,
- Pierre Cauchy1,
- Jason Piper2,
- Elisabeth Bertrand3,
- Naveen Lalli2,
- Rebecca C Jarvis1,
- Liam Niall Gilding1,
- Sascha Ott2,
- Constanze Bonifer1 and
- Peter N Cockerill*,1
- 1Institute of Biomedical Research, College of Medicine and Dentistry, University of Birmingham, Birmingham, UK
- 2Warwick Systems Biology Centre, University of Warwick, Coventry, UK
- 3Section of Experimental Haematology, Leeds Institute for Molecular Medicine, University of Leeds, Leeds, UK
- ↵*Corresponding author. Tel: +44 121 4146841; E‐mail: p.n.cockerill{at}bham.ac.uk
Naïve T cells become epigenetically imprinted when activated and stably maintain regions of accessible active chromatin to support efficient reactivation of genes in primed T cells.
Synopsis
Naïve T cells become epigenetically imprinted when activated and subsequently they stably maintain regions of accessible active chromatin bound by ETS1 and RUNX1. These primed DNA elements support efficient reactivation of inducible genes in previously activated T cells.
Naïve T cells acquire a specific epigenetic imprint after initial T‐cell activation.
Primed T cells and memory‐phenotype cells retain a subset of accessible chromatin sites as DNase I‐hypersensitive sites.
ETS‐1 and RUNX1 remain bound to primed DNase I‐hypersensitive sites in previously activated T cells.
Primed DNase I‐hypersensitive sites facilitate inducible enhancer function.
The EMBO Journal (2016) 35: 515–535
- Received July 13, 2015.
- Revision received December 18, 2015.
- Accepted December 22, 2015.
- © 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.
- Touch, act and go: landing and operating on nucleosomes
- 1Department of Biology and Biotechnology, University of Pavia, Pavia, Italy
- 2Division of Biochemistry and Cancer Genomics Center, Netherlands Cancer Institute, Amsterdam, The Netherlands
- ↵*Corresponding author. Tel: +39032985525; E‐mail: andrea.mattevi{at}unipv.it
This review summarizes the emerging structural understanding of nucleosome recognition by multiprotein readers, writers and erasers of chromatin marks, which are key for integrating information from both DNA and histone modifications.
The EMBO Journal (2016) 35: 376–388
- Received October 30, 2015.
- Revision received November 30, 2015.
- Accepted December 10, 2015.
- © 2016 The Authors
- Dissection of transcriptional and cis‐regulatory control of differentiation in human pancreatic cancer
- Giuseppe R Diaferia1,†,
- Chiara Balestrieri1,†,
- Elena Prosperini1,
- Paola Nicoli1,
- Paola Spaggiari2,
- Alessandro Zerbi2 and
- Gioacchino Natoli*,1
- 1Department of Experimental Oncology, European Institute of Oncology (IEO), Milan, Italy
- 2Division of Pancreatic Surgery, Humanitas Clinical Institute, Milan, Italy
- ↵*Corresponding author. Tel: +39 02 57489953; E‐mail: gioacchino.natoli{at}ieo.eu
↵† These authors contributed equally to this work (order determined by drawing)
By combining expression profiling, epigenomic footprinting and loss‐of‐function experiments, this work catalogues the differential usage of transcription factors and enhancers during tumor progression in human pancreatic ductal adenocarcinoma (PDAC).
Synopsis
By combining expression profiling, epigenomic footprinting and loss‐of‐function experiments, this work catalogues the differential usage of transcription factors and enhancers during tumor progression in human pancreatic ductal adenocarcinoma (PDAC).
Carcinomas show various degrees of histological deviation from the tissue they derive from (tumor grade).
Pancreatic ductal adenocarcinomas (PDACs) show great intra‐tumor grade heterogeneity, which determines a different sensitivity of cells of the same tumor to therapeutic agents.
The transcriptional and cis‐regulatory determinants of human low‐ and high‐grade PDACs were dissected through a combination of epigenomic, transcriptomic and genetic approaches.
Transcription factors and genomic regulatory sequences controlling differentiation of human PDACs were identified and validated.
Among them, KLF5 contributes to controlling the epithelial program and is required for the recruitment to cis‐regulatory elements of other transcription factors selectively expressed in low‐grade PDACs.
The EMBO Journal (2016) 35: 595–617
- Received June 30, 2015.
- Revision received December 3, 2015.
- Accepted December 7, 2015.
- © 2016 The Authors
- In need of good neighbours: transcription factors require local DNA hypomethylation for target binding
Whether and how DNA methylation influences the binding of transcription factors (TFs) to their corresponding DNA sequence motifs in vivo remains largely unresolved. In a recent publication, Schübeler and co‐workers (Domcke et al, 2015) identify a few methylation‐restricted TFs in mouse embryonic stem cells, including NRF1. The authors show that NRF1 binding to its motif can be outcompeted by de novo DNA methylation, suggesting that methylation‐sensitive TFs rely on neighbouring motifs in cis—bound by pioneer TFs—to ensure local hypomethylation.
See also: S Domcke et al (December 2015)
Transcription factors (TFs) bind only a subset of possible target sites in the genome, but the basis for this specificity has remained unclear. A new study shows DNA methylation to control target site access for specific transcription factors.
- © 2016 The Authors
- TET‐catalyzed oxidation of intragenic 5‐methylcytosine regulates CTCF‐dependent alternative splicing
- Ryan J Marina1,†,
- David Sturgill1,†,
- Marc A Bailly12†,
- Morgan Thenoz1,†,
- Garima Varma13,
- Maria F Prigge1,
- Kyster K Nanan1,
- Sanjeev Shukla14,
- Nazmul Haque15 and
- Shalini Oberdoerffer*,1
- 1Center for Cancer Research, Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, Bethesda, MD, USA
- 2Merck Research Laboratory, Palo Alto, CA, USA
- 3 Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA
- 4 Department of Biological Sciences, Indian Institute of Science Education and Research (IISER), Bhopal, India
- 5 National Heart, Lung and Blood Institute, Bethesda, MD, USA
- ↵*Corresponding author. Tel: +1 301 594 8151; Fax: +1 301 496 4951; E‐mail: shalini.oberdoerffer{at}nih.gov
↵† These authors contributed equally to this work
Variations in methylcytosine oxidation state are controlled by the activity of the TET enzymes. TET1/2 activity at intragenic regions allows for enhanced CTCF binding and stimulates the inclusion of alternative exons, thus adding further complexity to the splicing code.
Synopsis
Variations in methylcytosine oxidation state are controlled by the activity of the TET enzymes. TET1/2 activity at intragenic regions allows for enhanced CTCF binding and stimulates the inclusion of alternative exons, thus adding further complexity to the splicing code.
Overlapping methylation at CTCF‐binding sites allows for regulation of alternative pre‐mRNA splicing via variations in TET activity.
The TET proteins directly promote alternative exon inclusion by facilitating CTCF‐associated pol II pausing downstream of weak splice sites.
TET‐catalyzed 5hmC and 5caC are enriched at CTCF‐binding sites in cells and CTCF directly interacts with 5caC‐containing DNA in vitro.
Reduced TET activity results in 5mC‐coupled CTCF eviction and associated exclusion of weak exons from spliced mRNA.
The EMBO Journal (2016) 35: 335–355
- Received October 9, 2015.
- Revision received November 12, 2015.
- Accepted November 25, 2015.
- Published 2015. This article is a U.S. Government work and is in the public domain in the USA
- A hit‐and‐run heat shock factor governs sustained histone methylation and transcriptional stress memory
- 1Institute for Biochemistry and Biology, University of Potsdam, Potsdam, Germany
- 2Institute of Biology, Free University Berlin, Berlin, Germany
- ↵*Corresponding author. Tel: +49 331 9772647; E‐mail: isabel.baeurle{at}uni-potsdam.de
Stress exposure can prime for an enhanced response upon re‐exposure. In Arabidopsis, heat stress‐mediated priming is associated with stable histone H3 lysine 4 di‐ and trimethylation and requires transcription factor HSFA2 that only transiently binds to the primed gene loci.
Synopsis
Stress exposure can prime for an enhanced response upon re‐exposure. In Arabidopsis, heat stress‐mediated priming is associated with stable histone H3 lysine 4 di‐ and trimethylation and requires transcription factor HSFA2 that only transiently binds to the primed gene loci.
Heat stress primes genes for sustained activation and/or enhanced induction upon recurring stress.
This transcriptional memory is linked to induction of histone H3 lysine 4 di‐ and trimethylation.
Transcription factor HSFA2 is required for transcriptional memory.
HSFA2 only transiently associates with the gene loci, suggesting it acts in a hit‐and‐run mode.
The EMBO Journal (2016) 35: 162–175
- Received July 17, 2015.
- Revision received November 9, 2015.
- Accepted November 13, 2015.
- © 2015 The Authors
- BRPF3‐HBO1 regulates replication origin activation and histone H3K14 acetylation
- Yunpeng Feng1,8,†,
- Arsenios Vlassis1,†,
- Céline Roques2,†,
- Marie‐Eve Lalonde2,
- Cristina González‐Aguilera1,
- Jean‐Philippe Lambert3,
- Sung‐Bau Lee1,4,
- Xiaobei Zhao5,9,
- Constance Alabert1,
- Jens V Johansen1,
- Eric Paquet2,
- Xiang‐Jiao Yang6,
- Anne‐Claude Gingras3,7,
- Jacques Côté*,2 and
- Anja Groth*,1
- 1Biotech Research and Innovation Centre (BRIC) and Center for Epigenetics, University of Copenhagen, Copenhagen, Denmark
- 2St‐Patrick Research Group in Basic Oncology, Laval University Cancer Research Center, Oncology Axis‐CHU de Québec Research Center, Quebec City, QC, Canada
- 3Lunenfeld‐Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
- 4Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
- 5Bioinformatics Centre Department of Biology, University of Copenhagen, Copenhagen, Denmark
- 6Department of Medicine, McGill University Health Center, Montréal, QC, Canada
- 7Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada
- 8The Institute of Genetics and Cytology, Northeast Normal University, Changchun, China
- 9Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA
- ↵*
Corresponding author. Tel: +1 418 525 4444, poste 15545; E‐mail: jacques.cote{at}crhdq.ulaval.ca
Corresponding author. Tel: +45 3532 5538; E‐mail: anja.groth{at}bric.ku.dk
↵† These authors contributed equally to this work
An RNAi screen for chromatin regulators of replication control reveals an origin activation role of HBO1 acetyltransferase role that is separate from its function in origin licensing.
Synopsis
A distinct origin activation role of HBO1 acetyltransferase provides new insight into how demarcation of chromatin surrounding transcription start sites affects the regulation of nearby replication origins.
siRNA screen identifies chromatin regulators important for DNA replication, including the scaffold protein BRPF3.
BRPF3 regulates origin firing by directing the acetyltransferase HBO1 to target histone H3K14 in chromatin surrounding replication origins.
HBO1‐BRPF3 complex function in origin activation is separate from and complementary to HBO1‐JADE1 function in origin licensing.
Reduced origin activation upon BRPF3 depletion protects cells against replication stress‐induced DNA damage.
The EMBO Journal (2016) 35: 176–192
- Received February 16, 2015.
- Revision received October 30, 2015.
- Accepted November 3, 2015.
- © 2015 The Authors
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