Chemical biology

  • Article | | open

    Large-scale deletions of mitochondrial DNA (mtDNA) are associated with different human mitochondrial diseases and normal human ageing. Here the authors present a model for mtDNA formation based on generation sequencing analysis of patients samples and in vitro reconstituted mtDNA deletion using purified proteins.

    • Örjan Persson
    • , Yazh Muthukumar
    • , Swaraj Basu
    • , Louise Jenninger
    • , Jay P. Uhler
    • , Anna-Karin Berglund
    • , Robert McFarland
    • , Robert W. Taylor
    • , Claes M. Gustafsson
    • , Erik Larsson
    •  & Maria Falkenberg
  • Article | | open

    Investigation of a reaction scope usually starts with the optimization for a model substrate. Here, the authors apply a time-efficient multi-substrate screening approach to identify a general organocatalyst for the Diels–Alder reaction of cyclopentadiene with α,β-unsaturated aldehydes.

    • Hyejin Kim
    • , Gabriela Gerosa
    • , Jonas Aronow
    • , Pinar Kasaplar
    • , Jie Ouyang
    • , Julia B. Lingnau
    • , Paul Guerry
    • , Christophe Farès
    •  & Benjamin List
  • Article | | open

    SecB homologs can be associated with stress-responsive type II toxin–antitoxin (TA) systems and form tripartite toxin-antitoxin-chaperone systems (TAC). Here the authors provide structural insights into TACs by presenting the crystal structure of the M. tuberculosis TA-associated SecB chaperone in complex with the C-terminal ChAD (chaperone addiction) extension of the antitoxin HigA1.

    • Valérie Guillet
    • , Patricia Bordes
    • , Cécile Bon
    • , Julien Marcoux
    • , Virginie Gervais
    • , Ambre Julie Sala
    • , Suzana Dos Reis
    • , Nawel Slama
    • , Israel Mares-Mejía
    • , Anne-Marie Cirinesi
    • , Laurent Maveyraud
    • , Pierre Genevaux
    •  & Lionel Mourey
  • Article | | open

    Serine/threonine phosphatases such as PP1 associate with a large array of subunit proteins, such as ASPP (apoptosis-stimulating protein of p53) to achieve selective targeting. Here authors solved the crystal structure of the human ASPP2/PP1 complex and explain how ASPP2 can distinguish between PP1 isoforms.

    • M. Teresa Bertran
    • , Stéphane Mouilleron
    • , Yanxiang Zhou
    • , Rakhi Bajaj
    • , Federico Uliana
    • , Ganesan Senthil Kumar
    • , Audrey van Drogen
    • , Rebecca Lee
    • , Jennifer J. Banerjee
    • , Simon Hauri
    • , Nicola O’Reilly
    • , Matthias Gstaiger
    • , Rebecca Page
    • , Wolfgang Peti
    •  & Nicolas Tapon
  • Article | | open

    The antitermination factor RfaH adopts two functional states where its C-terminal domain is folded either as an α-helical hairpin or β-barrel. Here the authors employ solution state NMR measurements to show that the C-terminal domain transforms into the β-barrel only upon binding to the elongation complex and refolds back after dissociation.

    • Philipp Konrad Zuber
    • , Kristian Schweimer
    • , Paul Rösch
    • , Irina Artsimovitch
    •  & Stefan H. Knauer
  • Article | | open

    Ubiquitination may control protein stability or function. Here the authors show that an ubiquitination enzyme, Hectd3, ubiquitinates Stat3 and Malt1 to modulate their function but not degradation in T cells, and thereby promoting the differentiation of pathogenic Th17 cells and susceptibility to a mouse model of multiple sclerosis.

    • Jonathan J. Cho
    • , Zhiwei Xu
    • , Upasana Parthasarathy
    • , Theodore T. Drashansky
    • , Eric Y. Helm
    • , Ashley N. Zuniga
    • , Kyle J. Lorentsen
    • , Samira Mansouri
    • , Joshua Y. Cho
    • , Mariola J. Edelmann
    • , Duc M. Duong
    • , Torben Gehring
    • , Thomas Seeholzer
    • , Daniel Krappmann
    • , Mohammad N. Uddin
    • , Danielle Califano
    • , Rejean L. Wang
    • , Lei Jin
    • , Hongmin Li
    • , Dongwen Lv
    • , Daohong Zhou
    • , Liang Zhou
    •  & Dorina Avram
  • Article | | open

    How the chromosome passenger complex (CPC) phosphorylates the kinetochores that can be a micron away to control mitotic events is unknown. Here the authors find that the CPC directly binds microtubules near inner centromeres, which controls its ability to phosphorylate kinetochores independently of tension generated by kinetochore microtubule attachments.

    • Prasad Trivedi
    • , Anatoly V. Zaytsev
    • , Maxim Godzi
    • , Fazly I. Ataullakhanov
    • , Ekaterina L. Grishchuk
    •  & P. Todd Stukenberg
  • Article | | open

    Class F receptors are therapeutic targets in human disease and understanding their structural changes during receptor activation may provide important pharmacological insight. Here, the authors combine computational and experimental methods to identify a molecular switch in TM6/7 of Class F receptors that mediates receptor activation.

    • Shane C. Wright
    • , Paweł Kozielewicz
    • , Maria Kowalski-Jahn
    • , Julian Petersen
    • , Carl-Fredrik Bowin
    • , Greg Slodkowicz
    • , Maria Marti-Solano
    • , David Rodríguez
    • , Belma Hot
    • , Najeah Okashah
    • , Katerina Strakova
    • , Jana Valnohova
    • , M. Madan Babu
    • , Nevin A. Lambert
    • , Jens Carlsson
    •  & Gunnar Schulte
  • Article | | open

    Cryo-electron microscopy can determine the structure but not the nanomechanics of biological matter. Here the authors combine force spectroscopy in cryogenic conditions with computer simulations to characterize the properties of DNA simultaneously down to the sub-nm level.

    • Rémy Pawlak
    • , J. G. Vilhena
    • , Antoine Hinaut
    • , Tobias Meier
    • , Thilo Glatzel
    • , Alexis Baratoff
    • , Enrico Gnecco
    • , Rubén Pérez
    •  & Ernst Meyer
  • Article | | open

    Many 2-Cystein Peroxiredoxins (Prx) can either function as peroxidases or chaperones when exposed to stress. Here the authors present the structures of Leishmania infantum mitochondrial Prx alone and with a bound model client protein, use crosslinking to reveal interaction regions that stabilize the bound client, and provide insights into the mechanism by which Prx’s adopt chaperone activity.

    • Filipa Teixeira
    • , Eric Tse
    • , Helena Castro
    • , Karl A. T. Makepeace
    • , Ben A. Meinen
    • , Christoph H. Borchers
    • , Leslie B. Poole
    • , James C. Bardwell
    • , Ana M. Tomás
    • , Daniel R. Southworth
    •  & Ursula Jakob
  • Article | | open

    A fundamental step in membrane protein biogenesis is their integration into the lipid bilayer with a defined orientation of each transmembrane segment. Here, the authors show that mutations in connexin 32 can cause failures in membrane integration which is detected by the ER chaperone machinery.

    • João P. L. Coelho
    • , Matthias Stahl
    • , Nicolas Bloemeke
    • , Kevin Meighen-Berger
    • , Carlos Piedrafita Alvira
    • , Zai-Rong Zhang
    • , Stephan A. Sieber
    •  & Matthias J. Feige
  • Article | | open

    Many Gram-negative bacteria rely on a type III secretion system (T3SS) for their pathogenicity. Here authors present the cryo-EM structure of the E.coli T3SS ATPase-central stalk complex, which forms a homohexameric, asymmetric pore with different functional states.

    • Dorothy D. Majewski
    • , Liam J. Worrall
    • , Chuan Hong
    • , Claire E. Atkinson
    • , Marija Vuckovic
    • , Nobuhiko Watanabe
    • , Zhiheng Yu
    •  & Natalie C. J. Strynadka
  • Article | | open

    Elp3 is the catalytic subunit of the eukaryotic Elongator complex that catalyzes posttranscriptional tRNA modifications. Here the authors present the crystal structures of an acetyl-CoA analog bound bacterial Elp3 and a monomeric archaeal Elp3 and show that Elp3 functions as a tRNA modification enzyme in all domains of life.

    • Ting-Yu Lin
    • , Nour El Hana Abbassi
    • , Karol Zakrzewski
    • , Andrzej Chramiec-Głąbik
    • , Małgorzata Jemioła-Rzemińska
    • , Jan Różycki
    •  & Sebastian Glatt
  • Article | | open

    The FDA approved drug aprepitant is an antagonist of the Neurokinin 1 receptor (NK1R). Here the authors present aprepitant bound NK1R crystal structures and use NMR spectroscopy to gain further insights into the dynamics of aprepitant binding, which is of interest for further drug development.

    • Shuanghong Chen
    • , Mengjie Lu
    • , Dongsheng Liu
    • , Lingyun Yang
    • , Cuiying Yi
    • , Limin Ma
    • , Hui Zhang
    • , Qing Liu
    • , Thomas M. Frimurer
    • , Ming-Wei Wang
    • , Thue W. Schwartz
    • , Raymond C. Stevens
    • , Beili Wu
    • , Kurt Wüthrich
    •  & Qiang Zhao
  • Article | | open

    PTEN is a lipid phosphatase that functions as a dose-dependent tumor suppressor through the PI3K/AKT pathway. Here the authors describe a signaling feedback mechanism where PTEN stability is regulated through transcriptional upregulation of X-linked ubiquitin-specific protease 11 (USP11) via the PI3K/FOXO pathway.

    • Mi Kyung Park
    • , Yixin Yao
    • , Weiya Xia
    • , Stephanie Rebecca Setijono
    • , Jae Hwan Kim
    • , Isabelle K. Vila
    • , Hui-Hsuan Chiu
    • , Yun Wu
    • , Enrique González Billalabeitia
    • , Min Gyu Lee
    • , Robert G. Kalb
    • , Mien-Chie Hung
    • , Pier Paolo Pandolfi
    • , Su Jung Song
    •  & Min Sup Song
  • Article | | open

    Zinc ions (Zn2+) are imported by Golgi-resident transporters but the function of zinc in the early secretory pathway has remained unknown. Here the authors find that Zn2+ regulates protein quality control in the early secretory pathway by demonstrating that the pH-sensitive chaperone ERp44 binds Zn2+ and solving the Zn2+-bound ERp44 structure.

    • Satoshi Watanabe
    • , Yuta Amagai
    • , Sara Sannino
    • , Tiziana Tempio
    • , Tiziana Anelli
    • , Manami Harayama
    • , Shoji Masui
    • , Ilaria Sorrentino
    • , Momo Yamada
    • , Roberto Sitia
    •  & Kenji Inaba
  • Article | | open

    Antibodies against Plasmodium falciparum merozoites that fix complement can inhibit blood-stage replication. Here, Reiling et al. show that complement-fixing antibodies strongly correlate with protective immunity in children, identify the merozoite targets, and predict antigen combinations that should result in strong protection.

    • Linda Reiling
    • , Michelle J. Boyle
    • , Michael T. White
    • , Danny W. Wilson
    • , Gaoqian Feng
    • , Rupert Weaver
    • , D. Herbert Opi
    • , Kristina E. M. Persson
    • , Jack S. Richards
    • , Peter M. Siba
    • , Freya J. I. Fowkes
    • , Eizo Takashima
    • , Takafumi Tsuboi
    • , Ivo Mueller
    •  & James G. Beeson
  • Article | | open

    Thermally activated delayed fluorescence is a mechanism for enhancing the efficiency of organic light emitting diodes by harvesting triplet excitons, but there is still a need to design more efficient materials. Here, the authors rationally design and characterize a series of π-extended boron- and nitrogen-doped nanographenes as promising candidates.

    • Anton Pershin
    • , David Hall
    • , Vincent Lemaur
    • , Juan-Carlos Sancho-Garcia
    • , Luca Muccioli
    • , Eli Zysman-Colman
    • , David Beljonne
    •  & Yoann Olivier
  • Article | | open

    Kinetochore function depends on H4K20 monomethylation in centromeric nucleosomes but the underlying mechanism is unclear. Here, the authors provide evidence that the centromere-specific nucleosome subunit CENP-A facilitates H4K20 methylation by enabling a conformational change of the H4 N-terminal tail.

    • Yasuhiro Arimura
    • , Hiroaki Tachiwana
    • , Hiroki Takagi
    • , Tetsuya Hori
    • , Hiroshi Kimura
    • , Tatsuo Fukagawa
    •  & Hitoshi Kurumizaka
  • Article | | open

    The genomic locations that can be targeted for editing by CRISPR are limited by the presence of the nuclease-specific PAM sequence. Here, the authors show PAM recognition can be expanded by replacing the key region in the PAM interaction domain of SaCas9 with the corresponding region of SaCas9 orthologs.

    • Dacheng Ma
    • , Zhimeng Xu
    • , Zhaoyu Zhang
    • , Xi Chen
    • , Xiangzhi Zeng
    • , Yiyang Zhang
    • , Tingyue Deng
    • , Mengfei Ren
    • , Zheng Sun
    • , Rui Jiang
    •  & Zhen Xie
  • Article | | open

    Cross-dehydrogenative coupling (CDC) is a powerful method for C-C bond formation however the enantioselective variant is underdeveloped. Here, the authors show a formal enantioselective CDC method involving unactivated ethers and carboxylic acid derivatives allowing for the rapid preparation of biologically active molecules.

    • Gang Wang
    • , Xiaodong Xin
    • , Zehua Wang
    • , Gang Lu
    • , Yudao Ma
    •  & Lei Liu
  • Article | | open

    Producing individual cannabinoids by metabolically engineered microbes has proven challenging. Here, the authors develop a cell-free enzymatic prenylating system to generate isoprenyl pyrophosphate substrates directly from glucose and produce both common and rare cannabinoids at >1 g/L.

    • Meaghan A. Valliere
    • , Tyler P. Korman
    • , Nicholas B. Woodall
    • , Gregory A. Khitrov
    • , Robert E. Taylor
    • , David Baker
    •  & James U. Bowie
  • Article | | open

    Ribosome-associated quality control (RQC) pathways monitor and respond to stalling of the translating ribosome. Here the authors show that the ribosome associated RQC factor Hel2/ZNF598, an E3 ubiquitin ligase, generally interacts with mRNAs in the vicinity of stop codons.

    • Marie-Luise Winz
    • , Lauri Peil
    • , Tomasz W. Turowski
    • , Juri Rappsilber
    •  & David Tollervey
  • Article | | open

    Mother Nature is a valuable resource for the discovery of drug and agricultural chemicals. Here, the authors show that 7-deoxy-sedoheptulose produced by a cyanobacterium is an antimicrobial and herbicidal compound that acts through inhibition of 3-dehydroquniate synthase in the shikimate pathway.

    • Klaus Brilisauer
    • , Johanna Rapp
    • , Pascal Rath
    • , Anna Schöllhorn
    • , Lisa Bleul
    • , Elisabeth Weiß
    • , Mark Stahl
    • , Stephanie Grond
    •  & Karl Forchhammer
  • Article | | open

    The role of mesencephalic astrocyte-derived neurotrophic factor (MANF) in maintenance of protein folding homeostasis inside the ER has remained unclear. Here the authors determine the structure of the complex between MANF and the ER-localized chaperone BiP and provide evidence that MANF serves as an anti-nucleotide exchange factor for BiP.

    • Yahui Yan
    • , Claudia Rato
    • , Lukas Rohland
    • , Steffen Preissler
    •  & David Ron
  • Article | | open

    Synthetic chemists develop a "chemical intuition" over years of experience in the lab. Here the authors combine machine learning of (partially) failed experiments with robotic synthesis to capture this intuition used in searching for the optimal synthesis conditions of metal-organic frameworks.

    • Seyed Mohamad Moosavi
    • , Arunraj Chidambaram
    • , Leopold Talirz
    • , Maciej Haranczyk
    • , Kyriakos C. Stylianou
    •  & Berend Smit
  • Article | | open

    Highly enantioselective synthesis of allenes has been relying, so far, on the steric hindrance of substrates. Here the authors achieve excellent stereocontrol in the synthesis of chiral allenes with a palladium-DTBM-SEGPHOS catalytic system in a non-substrate-dependent manner.

    • Shihua Song
    • , Jing Zhou
    • , Chunling Fu
    •  & Shengming Ma
  • Article | | open

    Combination therapy for Buruli ulcer (BU) is suboptimal. Here, Liu et al. show that the candidate drug TB47 has potent bactericidal activity against Mycobacterium ulcerans in vitro and in a mouse model, which underscores its potential for shortening the course of BU and treating other mycobacterial diseases.

    • Yang Liu
    • , Yamin Gao
    • , Jianxiong Liu
    • , Yaoju Tan
    • , Zhiyong Liu
    • , Chiranjibi Chhotaray
    • , Huofeng Jiang
    • , Zhili Lu
    • , Gift Chiwala
    • , Shuai Wang
    • , Gaelle Makafe
    • , Md Mahmudul Islam
    • , H. M. Adnan Hameed
    • , Xingshan Cai
    • , Changwei Wang
    • , Xinjie Li
    • , Shouyong Tan
    •  & Tianyu Zhang
  • Article | | open

    Membraneless compartments have been theorized to be prebiotic micro-compartments as they spontaneously encapsulate RNA and proteins. Here, the authors report membraneless compartments can enhance RNA chemistries, affecting template directed RNA polymerization and stimulating nucleic acid enzymes.

    • Raghav R. Poudyal
    • , Rebecca M. Guth-Metzler
    • , Andrew J. Veenis
    • , Erica A. Frankel
    • , Christine D. Keating
    •  & Philip C. Bevilacqua
  • Article | | open

    IRSp53 is a key regulator of filopodia formation and cell migration. Here, the authors elucidate a mechanism of phosphorylation-dependent inhibition of IRSp53 by 14-3-3, which impedes the interactions of IRSp53 with membranes and downstream cytoskeletal effectors.

    • David J. Kast
    •  & Roberto Dominguez
  • Article | | open

    The origin and physiological significance of lipid droplets (LDs) in the nucleus is not clear. Here authors show that nucleoplasmic LDs in hepatocytes are derived from apolipoprotein B (ApoB)-free lumenal LDs and constitute a feedback mechanism to regulate PC synthesis in accordance with ER stress.

    • Kamil Sołtysik
    • , Yuki Ohsaki
    • , Tsuyako Tatematsu
    • , Jinglei Cheng
    •  & Toyoshi Fujimoto
  • Article | | open

    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
    • , Katherine Newling
    • , Rebeca Ridings-Figueroa
    • , Victoria Scott
    • , Peter D. Ashton
    • , Justin F. X. Ainscough
    •  & Dawn Coverley
  • Article | | open

    Genetic logic devices allow the host cell to incorporate multiple inputs to determine output behaviour. Here the authors provide a framework for engineering reliable recombinase-based devices and demonstrate 4-input logic in a multicellular system.

    • Sarah Guiziou
    • , Pauline Mayonove
    •  & Jerome Bonnet
  • Article | | open

    Designing interfaces that can induce protein-protein interactions is a challenging problem. Here the authors show that a five amino acid sequence known to mediate domain swapping in cystatins can drive oligomerization when grafted onto functionally and structurally unrelated host proteins, providing a simple approach to the design of protein assemblies.

    • Neha Nandwani
    • , Parag Surana
    • , Hitendra Negi
    • , Nahren M. Mascarenhas
    • , Jayant B. Udgaonkar
    • , Ranabir Das
    •  & Shachi Gosavi
  • Article | | open

    While the conversion of greenhouse CO2 to chemical fuels offers a promising renewable energy technology, there is a dire need for new materials. Here, authors report the largest CO2 photocathode search using a first-principles approach to identify both known and unreported candidate photocatalysts.

    • Arunima K. Singh
    • , Joseph H. Montoya
    • , John M. Gregoire
    •  & Kristin A. Persson
  • Article | | open

    Bacterial cellulose (BC) is a ubiquitous biomaterial, but functionalization relies on modification processes which have low reaction efficiency and can cause pollution. Here the authors develop an environmental friendly in-situ fermentation method using fluorescein labelled glucose to produce fluorescent BC.

    • Minghong Gao
    • , Juan Li
    • , Zixian Bao
    • , Moudong Hu
    • , Rui Nian
    • , Dexin Feng
    • , Dong An
    • , Xing Li
    • , Mo Xian
    •  & Haibo Zhang
  • Article | | open

    The incomplete nature and undefined structure of the existing catalysis research data has prevented comprehensive knowledge extraction. Here, the authors report a novel meta-analysis method that identifies correlations between a catalyst’s physico-chemical properties and its performance in a particular reaction.

    • Roman Schmack
    • , Alexandra Friedrich
    • , Evgenii V. Kondratenko
    • , Jörg Polte
    • , Axel Werwatz
    •  & Ralph Kraehnert
  • Article | | open

    The chaperone Hsp90 is a potential target for the development of drugs against fungal pathogens. Here the authors determine the structure of the Hsp90 nucleotide-binding domain from Candida albicans, which they use to design an inhibitor and demonstrate its selectivity for the fungal enzyme, both biochemically and in cells.

    • Luke Whitesell
    • , Nicole Robbins
    • , David S. Huang
    • , Catherine A. McLellan
    • , Tanvi Shekhar-Guturja
    • , Emmanuelle V. LeBlanc
    • , Catherine S. Nation
    • , Raymond Hui
    • , Ashley Hutchinson
    • , Cathy Collins
    • , Sharanya Chatterjee
    • , Richard Trilles
    • , Jinglin L. Xie
    • , Damian J. Krysan
    • , Susan Lindquist
    • , John A. Porco Jr.
    • , Utpal Tatu
    • , Lauren E. Brown
    • , Juan Pizarro
    •  & Leah E. Cowen
  • Article | | open

    Hippo signaling leads to the phosphorylation of the key transcriptional effector, Yap/Yki, although how Yap/Yki stability is regulated has remained unclear. Here, Sun et al. identify HAUSP/Usp7 as a conserved and clinically relevant regulator of the Hippo pathway that increases Yap/Yki stability.

    • Xiaohan Sun
    • , Yan Ding
    • , Meixiao Zhan
    • , Yan Li
    • , Dongqing Gao
    • , Guiping Wang
    • , Yang Gao
    • , Yong Li
    • , Shian Wu
    • , Ligong Lu
    • , Qingxin Liu
    •  & Zizhang Zhou
  • Article | | open

    Plants are dependent on controlled sugar uptake via Monosaccharide Transporters, such as STP10, for correct organ development, sugar accumulation in fruits and microbial defense. Here authors present the crystal structure of STP10 bound to glucose which sheds light on the fundamental principles of sugar transport in the plant-unique MST superfamily.

    • Peter Aasted Paulsen
    • , Tânia F. Custódio
    •  & Bjørn Panyella Pedersen
  • Article | | open

    Little is known about the degradation pathway of cyclic imines that are frequently found in bioactive secondary metabolites. Here, the authors found and characterised a copper amine oxidase, HarA that catalyses a ring-opening reaction of cyclic imine in harmaline and oxidative deamination of amines.

    • Toshiki Nagakubo
    • , Takuto Kumano
    • , Takehiro Ohta
    • , Yoshiteru Hashimoto
    •  & Michihiko Kobayashi
  • Article | | open

    The connection between DNA replication timing and changes that occur to the epigenome in cancer are still poorly understood. Here, the authors perform Repli-Seq and integrated epigenome analyses and find that genomic regions that undergo long-range epigenetic deregulation in prostate cancer also show concordant differences in replication timing.

    • Qian Du
    • , Saul A. Bert
    • , Nicola J. Armstrong
    • , C. Elizabeth Caldon
    • , Jenny Z. Song
    • , Shalima S. Nair
    • , Cathryn M. Gould
    • , Phuc-Loi Luu
    • , Timothy Peters
    • , Amanda Khoury
    • , Wenjia Qu
    • , Elena Zotenko
    • , Clare Stirzaker
    •  & Susan J. Clark
  • Article | | open

    The Cas12b family of CRISPR nucleases has been underutilized in mammalian cells due to the high temperature requirement of known members. Here the authors engineer BhCas12b to overcome this limitation for robust and specific genome editing applications in human cells.

    • Jonathan Strecker
    • , Sara Jones
    • , Balwina Koopal
    • , Jonathan Schmid-Burgk
    • , Bernd Zetsche
    • , Linyi Gao
    • , Kira S. Makarova
    • , Eugene V. Koonin
    •  & Feng Zhang
  • Article | | open

    Somatic alterations in the exonuclease domain of DNA polymerase ɛ have been linked to the development of highly mutated cancers. Here, the authors report that a major consequence of the most common cancer-associated Polɛ variant is a dramatically increased DNA polymerase activity.

    • Xuanxuan Xing
    • , Daniel P. Kane
    • , Chelsea R. Bulock
    • , Elizabeth A. Moore
    • , Sushma Sharma
    • , Andrei Chabes
    •  & Polina V. Shcherbakova
  • Article | | open

    The transcription factor Foxp3 and Stat5 modulate lineage stability and function of regulatory T (Treg) cells to promote immune homeostasis. Here the authors show that O-GlcNAcylation of Foxp3 and Stat5, mediated by O-GlcNAc transferase (OGT), is essential for Treg-mediate immune balance, with Treg-specific deficiency of OGT leading to severe autoimmunity.

    • Bing Liu
    • , Oscar C. Salgado
    • , Sangya Singh
    • , Keli L. Hippen
    • , Jason C. Maynard
    • , Alma L. Burlingame
    • , Lauren E. Ball
    • , Bruce R. Blazar
    • , Michael A. Farrar
    • , Kristin A. Hogquist
    •  & Hai-Bin Ruan
  • Article | | open

    In Drosophila, the Calypso–ASX complex catalyzes H2A deubiquitination and aids Polycomb in transcriptional silencing. Here the authors show that the orthologous complex, BAP1.com, promotes gene activation by counteracting PRC1-mediated gene silencing.

    • Antoine Campagne
    • , Ming-Kang Lee
    • , Dina Zielinski
    • , Audrey Michaud
    • , Stéphanie Le Corre
    • , Florent Dingli
    • , Hong Chen
    • , Lara Z. Shahidian
    • , Ivaylo Vassilev
    • , Nicolas Servant
    • , Damarys Loew
    • , Eric Pasmant
    • , Sophie Postel-Vinay
    • , Michel Wassef
    •  & Raphaël Margueron
  • Article | | open

    Early human embryonic development involves extensive changes in chromatin structure and transcriptional activity. Here the authors present LiCAT-seq, a method enabling simultaneous profiling of chromatin accessibility and gene expression with ultra-low input of cells and map chromatin accessibility and transcriptome landscapes for human pre-implantation embryos.

    • Longqi Liu
    • , Lizhi Leng
    • , Chuanyu Liu
    • , Changfu Lu
    • , Yue Yuan
    • , Liang Wu
    • , Fei Gong
    • , Shuoping Zhang
    • , Xiaoyu Wei
    • , Mingyue Wang
    • , Lei Zhao
    • , Liang Hu
    • , Jian Wang
    • , Huanming Yang
    • , Shida Zhu
    • , Fang Chen
    • , Guangxiu Lu
    • , Zhouchun Shang
    •  & Ge Lin
  • Article | | open

    Prion-forming proteins have been found in animals, plants, fungi, and bacteria. Here, Nan et al. report that a baculovirus-encoded protein behaves as prion in a yeast system and forms aggregates at high multiplicity of infection in insect cells that affect baculovirus replication.

    • Hao Nan
    • , Hongying Chen
    • , Mick F. Tuite
    •  & Xiaodong Xu