Featured
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Article |
Effect of natural genetic variation on enhancer selection and function
Naturally occurring genetic variation between inbred mouse strains is used as a mutagenesis strategy to investigate mechanisms responsible for the selection and function of cis-regulatory elements in macrophages; lineage-determining transcription factors are proposed to select enhancer-like regions in the genome in a collaborative fashion and facilitate the binding of signal-dependent factors.
- S. Heinz
- , C. E. Romanoski
- & C. K. Glass
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Letter |
MBNL proteins repress ES-cell-specific alternative splicing and reprogramming
This study identifies MBNL proteins as negative regulators of alternative splicing events that are differentially regulated between ES cells and other cell types; several lines of evidence show that these proteins repress an ES cell alternative splicing program and the reprogramming of somatic cells to induced pluripotent stem cells.
- Hong Han
- , Manuel Irimia
- & Benjamin J. Blencowe
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Letter |
TET2 promotes histone O-GlcNAcylation during gene transcription
TET2 is shown to associate with OGT, which catalyses O-GlcNAcylation, and the two enzymes are found together at transcription start sites; TET2 facilitates the activity of OGT in O-GlcNAcylation of histone 2B, and epigenetic modifications to both DNA and histones by TET2 and OGT may be important in gene transcription regulation.
- Qiang Chen
- , Yibin Chen
- & Xiaochun Yu
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Letter |
DNA-repair scaffolds dampen checkpoint signalling by counteracting the adaptor Rad9
DNA damage or replication stress induces the activation of checkpoint kinases, pausing the cell cycle so that DNA repair can take place; checkpoint activation must be regulated to prevent the cell-cycle arrest from persisting after damage is repaired, and now the Slx4–Rtt107 complex is shown to regulate checkpoint kinase activity by directly monitoring DNA-damage signalling.
- Patrice Y. Ohouo
- , Francisco M. Bastos de Oliveira
- & Marcus B. Smolka
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Letter |
Fucose sensing regulates bacterial intestinal colonization
FusKR, a fucose-sensing two-component system, has been identified in enterohaemorrhagic E. coli, linking fucose utilization and virulence factor gene expression and providing insight into how sensing of a host signal can facilitate bacterial colonization.
- Alline R. Pacheco
- , Meredith M. Curtis
- & Vanessa Sperandio
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Letter |
Tet1 controls meiosis by regulating meiotic gene expression
A loss-of-function approach in mice is used to show that the methylcytosine dioxygenase Tet1 has a role in regulating meiosis and meiotic gene activation in female germ cells; Tet1 deficiency does not greatly affect genome-wide demethylation but has a more specific effect on the expression of a subset of meiotic genes.
- Shinpei Yamaguchi
- , Kwonho Hong
- & Yi Zhang
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Letter |
B12 cofactors directly stabilize an mRNA regulatory switch
The crystal structures of two different cobalamin (vitamin B12)-binding riboswitches are determined; the structures reveal how cobalamin facilitates interdomain interactions to regulate gene expression.
- James E. Johnson Jr
- , Francis E. Reyes
- & Robert T. Batey
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Letter |
Set2 methylation of histone H3 lysine 36 suppresses histone exchange on transcribed genes
In yeast, histone H3 lysine 36 methylation can suppress the incorporation of acetylated histones by inhibiting histone exchange in transcribed genes, thus preventing spurious cryptic transcripts from initiating within open reading frames.
- Swaminathan Venkatesh
- , Michaela Smolle
- & Jerry L. Workman
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Letter |
Bacterial virulence proteins as tools to rewire kinase pathways in yeast and immune cells
Virulence factors from two bacteria are used to reprogram intracellular signalling in yeast and immune T cells, illustrating how pathogens can provide a toolkit to engineer cells for biotechnological or therapeutic applications.
- Ping Wei
- , Wilson W. Wong
- & Wendell A. Lim
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Letter |
SHARP1 suppresses breast cancer metastasis by promoting degradation of hypoxia-inducible factors
SHARP1, which is itself regulated by the p63 metastasis suppressor, regulates the invasive and metastatic phenotype in triple-negative breast cancer (TNBC) through inhibition of hypoxia-inducible factors, and this process operates independently from oxygen levels.
- Marco Montagner
- , Elena Enzo
- & Stefano Piccolo
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Letter |
A map of the cis-regulatory sequences in the mouse genome
A genomic map of nearly 300,000 potential cis-regulatory sequences determined from diverse mouse tissues and cell types reveals active promoters, enhancers and CCCTC-binding factor sites encompassing 11% of the mouse genome and significantly expands annotation of mammalian regulatory sequences.
- Yin Shen
- , Feng Yue
- & Bing Ren
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Article |
Embryonic stem cell potency fluctuates with endogenous retrovirus activity
A rare cell subpopulation within mouse embryonic stem cell cultures is identified that exhibits properties of two-cell (2C) embryos; the interconversion of ES cells to 2C cells correlates with endogenous retroviral activity.
- Todd S. Macfarlan
- , Wesley D. Gifford
- & Samuel L. Pfaff
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Article |
Fluoride ion encapsulation by Mg2+ ions and phosphates in a fluoride riboswitch
A riboswitch that binds fluoride was identified recently, which is surprising because both RNA and fluoride are negatively charged; here it is shown that the fluoride ion is coordinated to three positively charged magnesium ions, which are further encased in a negatively charged shell of RNA backbone phosphates and water molecules.
- Aiming Ren
- , Kanagalaghatta R. Rajashankar
- & Dinshaw J. Patel
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Letter |
A unifying model for mTORC1-mediated regulation of mRNA translation
mTORC1 is shown to regulate a translational program that requires the rapamycin-resistant 4E-BP family of translational repressors and consists almost entirely of mRNAs containing 5′ terminal oligopyrimidine or related motifs.
- Carson C. Thoreen
- , Lynne Chantranupong
- & David M. Sabatini
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Letter |
A novel putative auxin carrier family regulates intracellular auxin homeostasis in plants
The identification of PILS proteins, putative auxin transport facilitators, suggests that intracellular auxin transport might be evolutionarily older than directional, cell-to-cell PIN-dependent auxin transport, and highlights the developmental importance of intracellular auxin transport.
- Elke Barbez
- , Martin Kubeš
- & Jürgen Kleine-Vehn
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Research Highlights |
MicroRNAs boost gene variation
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Letter |
Spatial partitioning of the regulatory landscape of the X-inactivation centre
High-order chromatin folding in topologically associating domains has a critical role in proper long-range transcriptional control around the Xist locus, and presumably throughout the genome.
- Elphège P. Nora
- , Bryan R. Lajoie
- & Edith Heard
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Letter |
Systematic discovery of structural elements governing stability of mammalian messenger RNAs
Secondary structures, or pairing of complementary sequences within RNA, can regulate the binding of proteins that affect transcript stability, splicing, localization, and translation; a computational approach has now been used to discover secondary structures that affect global RNA stability through the binding of specific RNA binding proteins.
- Hani Goodarzi
- , Hamed S. Najafabadi
- & Saeed Tavazoie
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Research Highlights |
Noncoding RNAs decapped
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Review Article |
Modular regulatory principles of large non-coding RNAs
- Mitchell Guttman
- & John L. Rinn
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Letter |
The microRNA miR-34 modulates ageing and neurodegeneration in Drosophila
The conserved microRNA miR-34 regulates age-associated events and long-term brain integrity in Drosophila, providing a molecular link between ageing and neurodegeneration.
- Nan Liu
- , Michael Landreh
- & Nancy M. Bonini
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Letter |
Functional dissection of lysine deacetylases reveals that HDAC1 and p300 regulate AMPK
Genetic interaction profiles of human lysine deacetylases are generated by RNA interference knockdown to reveal the involvement of deacetylases in many critical biological processes, including metabolism, the cell cycle and development.
- Yu-yi Lin
- , Samara Kiihl
- & Jef D. Boeke
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Review Article |
The contribution of bone to whole-organism physiology
- Gérard Karsenty
- & Mathieu Ferron
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Letter |
Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis
Acute exercise is shown to induce autophagy in skeletal muscle of fed mice, indicating a possible mechanism for the beneficial metabolic effects of exercise.
- Congcong He
- , Michael C. Bassik
- & Beth Levine
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News & Views |
Drugs to awaken a paternal gene
Mutations in the maternal copy of the UBE3A gene cause a neurodevelopmental disorder known as Angelman syndrome. Drugs that activate the normally silenced paternal copy of this gene may be of therapeutic value. See Letter p.185
- Arthur L. Beaudet
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Letter |
Topoisomerase inhibitors unsilence the dormant allele of Ube3a in neurons
Cancer drugs that can potentially treat Angelman syndrome are identified.
- Hsien-Sung Huang
- , John A. Allen
- & Benjamin D. Philpot
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Article |
DNA-binding factors shape the mouse methylome at distal regulatory regions
Base-pair-resolution genomic maps of DNA methylation are generated in the mouse, providing new insights in gene regulation.
- Michael B. Stadler
- , Rabih Murr
- & Dirk Schübeler
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News & Views |
The clock within
The molecular clock machinery regulates organisms' responses to daily variations in the environment. One unexpected response seems to be temporal fine-tuning of stem-cell behaviour in the skin. See Article p.209
- Lorena Aguilar-Arnal
- & Paolo Sassone-Corsi
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Letter |
Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation
- Weiwei Yang
- , Yan Xia
- & Zhimin Lu
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Research Highlights |
Genetic switch for big muscles
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Letter |
Spalt mediates an evolutionarily conserved switch to fibrillar muscle fate in insects
- Cornelia Schönbauer
- , Jutta Distler
- & Frank Schnorrer
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Letter |
Regulatory evolution through divergence of a phosphoswitch in the transcription factor CEBPB
- Vincent J. Lynch
- , Gemma May
- & Günter P. Wagner
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News |
Smoking stokes cocaine cravings
Molecular mechanism found for controversial 'gateway drug' hypothesis.
- Virginia Gewin
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Letter |
Temporal dynamics and genetic control of transcription in the human prefrontal cortex
- Carlo Colantuoni
- , Barbara K. Lipska
- & Joel E. Kleinman
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Research Highlights |
Two-faced cancer gene
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Article
| Open Access
Mouse genomic variation and its effect on phenotypes and gene regulation
- Thomas M. Keane
- , Leo Goodstadt
- & David J. Adams
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Letter |
Polyamine sensing by nascent ornithine decarboxylase antizyme stimulates decoding of its mRNA
- Leo Kurian
- , R. Palanimurugan
- & R. Jürgen Dohmen
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Letter |
Architecture of the Mediator head module
- Tsuyoshi Imasaki
- , Guillermo Calero
- & Yuichiro Takagi
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Letter |
XUTs are a class of Xrn1-sensitive antisense regulatory non-coding RNA in yeast
- E. L. van Dijk
- , C. L. Chen
- & A. Morillon
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Letter |
MicroRNAs 103 and 107 regulate insulin sensitivity
- Mirko Trajkovski
- , Jean Hausser
- & Markus Stoffel
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News & Views |
Tet proteins in the limelight
Tet proteins mediate the hydroxymethylation of DNA. New work reveals their function in gene regulation and the extent of their activity throughout the genome of embryonic stem cells. See Article p.343 & Letters p.389, p.394 & p.398
- Nathalie Véron
- & Antoine H. F. M. Peters
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Article |
Global quantification of mammalian gene expression control
- Björn Schwanhäusser
- , Dorothea Busse
- & Matthias Selbach
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Letter |
COP1 is a tumour suppressor that causes degradation of ETS transcription factors
- Alberto C. Vitari
- , Kevin G. Leong
- & Vishva M. Dixit
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Letter |
Differential microRNA regulation of HLA-C expression and its association with HIV control
- Smita Kulkarni
- , Ram Savan
- & Mary Carrington
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Article |
TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity
- Kristine Williams
- , Jesper Christensen
- & Kristian Helin
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Letter |
CPEB and two poly(A) polymerases control miR-122 stability and p53 mRNA translation
- David M. Burns
- , Andrea D’Ambrogio
- & Joel D. Richter
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Letter |
Dual functions of Tet1 in transcriptional regulation in mouse embryonic stem cells
- Hao Wu
- , Ana C. D’Alessio
- & Yi Zhang
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Letter |
A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression
Long intergenic non-coding RNAs (lincRNAs) have been implicated in both gene silencing and activation, and could be a means for long-range control of gene expression. Here a lincRNA termed HOTTIP is identified at the 5′ tip of the HOXA locus that coordinates the activation of multiple 5′ HOXA genes. Chromosomal looping brings HOTTIP into the proximity of its target genes, where it seems to be required to facilitate histone H3 lysine 4 trimethylation and gene transcription.
- Kevin C. Wang
- , Yul W. Yang
- & Howard Y. Chang
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Letter |
Lifespan extension induced by AMPK and calcineurin is mediated by CRTC-1 and CREB
Activating AMPK or inactivating calcineurin slows ageing in worms and increases their lifespan. Here it is shown that inhibition of CRTC-1 is required for these life-extending effects. CRTC-1 is the only worm member in the family of CREB-regulated transcriptional co-activators, or CRTCs, and, like the mammalian family members, CRTC-1 interacts with a worm homologue of the CREB transcription factor (CRH-1). Eliminating crtc-1 increases lifespan in a crh-1-dependent manner, as does elimination of crh-1 alone. Downregulation of components in the CRTC/CREB pathway has previously been shown to confer health benefits to mice, complementing their lifespan effects in worms.
- William Mair
- , Ianessa Morantte
- & Andrew Dillin
The nuclear receptor Rev-erbα controls circadian thermogenic plasticity