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| Open AccessCombining Spinach-tagged RNA and gene localization to image gene expression in live yeast
Measuring single-cell mRNA dynamics is critical to understand gene expression. Here, using RNA Spinach technique to detect very low abundant mRNAs, Guet et al. report an analysis of the osmotic shock response in live yeast by localizing induced transcription factors, target gene loci and corresponding transcripts.
- David Guet
- , Laura T. Burns
- & Catherine Dargemont
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Article
| Open AccessRecombinase-based conditional and reversible gene regulation via XTR alleles
Synthetic biology can be used to regulate target genes and uncover gene function in physiologically relevant settings. Here Robles-Oteiza et al. describe a new recombinase-based system for conditional inactivation and inducible restoration of gene function and develop new mouse models to study p53 and Rb.
- Camila Robles-Oteiza
- , Sarah Taylor
- & David M. Feldser
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| Open AccessOscillation of p38 activity controls efficient pro-inflammatory gene expression
The prolonged presence of cytokines is necessary to produce a robust pro-inflammatory response through the activation of p38 MAPK. Here, Tomidaet al. show that asynchronous oscillatory activation of p38 MAPK occurs at the single-cell level and is necessary for the proper expression of pro-inflammatory genes.
- Taichiro Tomida
- , Mutsuhiro Takekawa
- & Haruo Saito
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| Open AccessThe fatty acid elongase Bond is essential for Drosophila sex pheromone synthesis and male fertility
Insect behaviours are often guided by chemical signals, but little is known about how pheromone diversity evolves. Here the authors show that loss of the gene bond in Drosophilaeliminates the sex pheromone CH503, while silencing it reduces the fertility of males and their conspecific rivals.
- Wan Chin Ng
- , Jacqueline S. R. Chin
- & Joanne Y. Yew
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| Open AccessIncreased COUP-TFII expression in adult hearts induces mitochondrial dysfunction resulting in heart failure
Transcription factor COUP-TFII is elevated in the hearts of non-ischaemic cardiomyopathy patients, but the nature of this correlation is unknown. Here the authors show that forced cardiac expression of COUP-TFII in mice causes dilated cardiomyopathy because of altered mitochondrial function and impaired metabolic remodelling.
- San-Pin Wu
- , Chung-Yang Kao
- & Sophia Y. Tsai
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Article
| Open AccessThe photochemical mechanism of a B12-dependent photoreceptor protein
Coenzyme B12 traditionally acts as cofactor to light-independent metabolic enzymes in bacteria and humans. Here, Kutta et al.present a time-resolved photochemical description of a B12-dependent photoreceptor protein, which represents a mechanistic foundation for B12 photobiology.
- Roger J. Kutta
- , Samantha J. O. Hardman
- & Alex R. Jones
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Article
| Open AccessRepression of arterial genes in hemogenic endothelium is sufficient for haematopoietic fate acquisition
The first haematopoietic stem and progenitor cells arise from the hemogenic endothelium of arterial vascular beds. Here the authors describe the mechanism that regulates the endothelial-to-haematopoietic transition and show that Sox17 and Notch1, genes critical to arterial endothelium identity, are also crucial repressors of haematopoietic fate.
- Carlos O. Lizama
- , John S. Hawkins
- & Ann C. Zovein
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| Open AccessDNA methylation of oestrogen-regulated enhancers defines endocrine sensitivity in breast cancer
The molecular factors influencing patient response to endocrine therapy are poorly understood. Here Stone et al.characterize the DNA methylome of endocrine response and show that methylation of oestrogen receptor-associated enhancers underpins endocrine sensitivity in human breast cancer.
- Andrew Stone
- , Elena Zotenko
- & Susan J. Clark
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| Open AccessA post-transcriptional mechanism pacing expression of neural genes with precursor cell differentiation status
Nervous system development relies on coherent up-regulation of extensive genes in a precise spatiotemporal manner. Here, the authors show that miR-9/TTP circuitry ensures coordinated up-regulation of neuronal mRNAs in neurons and limits unscheduled accumulation of these transcripts in non-neuronal cells.
- Weijun Dai
- , Wencheng Li
- & Eugene V. Makeyev
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| Open AccessWidespread seasonal gene expression reveals annual differences in human immunity and physiology
Infectious and chronic diseases display seasonal patterns, yet seasonal changes in physiology are rarely thought to affect human health. Here the authors show seasonal variation in all major blood cells and in gene and protein expression in diverse tissues, suggesting a mechanism for seasonal disease proneness and physiology.
- Xaquin Castro Dopico
- , Marina Evangelou
- & John A. Todd
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| Open AccessExpression of heterologous sigma factors enables functional screening of metagenomic and heterologous genomic libraries
Screening genomic or metagenomic libraries for interesting products or activities is often hampered by poor gene expression in a heterologous host. Here the authors show that the expression of a Lactobacillus sigma factor greatly enhances transcription of heterologous and environmental DNA in E. coli.
- Stefan M. Gaida
- , Nicholas R. Sandoval
- & Eleftherios T. Papoutsakis
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The molecular landscape of colorectal cancer cell lines unveils clinically actionable kinase targets
Precision oncology relies on model systems that reflect the genomic heterogeneity of human cancers. Here the authors characterize a panel of 151 colorectal cancer cell lines with respect to genetic mutations, expression profiles and drug sensitivity to identify new therapeutic targets.
- Enzo Medico
- , Mariangela Russo
- & Alberto Bardelli
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| Open AccessAblation of the p16INK4a tumour suppressor reverses ageing phenotypes of klotho mice
The protein p16INK4a promotes senescence in tissue stem cells and thereby contributes to organismal ageing. Here the authors reveal that p16INK4a also downregulates expression of a-klotho, thereby revealing an additional ageing-promoting function of 16INK4athat is independent from its role in senescence.
- Seidai Sato
- , Yuka Kawamata
- & Eiji Hara
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Lineage specification of ovarian theca cells requires multicellular interactions via oocyte and granulosa cells
Lineage establishment of theca cells is essential for follicle development and morphogenesis of the ovary. Here the authors provide genetic evidence for the origins of theca progenitor cells and study the mechanisms critical for their differentiation.
- Chang Liu
- , Jia Peng
- & Humphrey H.-C. Yao
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Article
| Open AccessA STIM2 splice variant negatively regulates store-operated calcium entry
STIM proteins sense calcium depletion in the endoplasmic reticulum and in response activate calcium influx through Orai1 channels located at the plasma membrane. Here, Miederer et al. identify a novel splice variant of STIM2 that fails to interact with and activate Orai1 and may act to fine-tune cellular calcium homeostasis by negatively regulating calcium influx.
- Anna-Maria Miederer
- , Dalia Alansary
- & Barbara A. Niemeyer
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An IL-27/NFIL3 signalling axis drives Tim-3 and IL-10 expression and T-cell dysfunction
Tim-3 is an inhibitory molecule that suppresses T-cell responses. Here the authors show that the cytokine IL-27, acting through the transcription factor NFIL3, induces Tim-3 in vivo, and that IL-27-conditioned Th1 cells have poor effector function.
- Chen Zhu
- , Kaori Sakuishi
- & Vijay K. Kuchroo
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| Open AccessWidespread sex differences in gene expression and splicing in the adult human brain
Men and women differ in terms of their neurochemistry, behaviour and susceptibility to disease. Here the authors show that sex differences in gene expression and splicing are widespread in adult human brain, and that sex-biased expression is likely to have functional consequences.
- Daniah Trabzuni
- , Adaikalavan Ramasamy
- & Mina Ryten
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Fluid flow and interlinked feedback loops establish left–right asymmetric decay of Cerl2 mRNA
During embryonic development, midline fluid flow results in asymmetric nodal gene expression. Using genetic manipulations and mathematical modelling, Nakamura et al. find that expression of the nodal antagonist Cerl2 is regulated post-transcriptionally, and that asymmetry is maintained by Wnt-Cerl2 feedback loops.
- Tetsuya Nakamura
- , Daisuke Saito
- & Hiroshi Hamada
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| Open AccessEscherichia coli noncoding RNAs can affect gene expression and physiology of Caenorhabditis elegans
It is known that differences in the bacterial food ofCaenorhabditis elegans can alter their behaviour. In this study, bacteria expressing two different noncoding RNAs alter the chemosensory and longevity of C. elegans, suggesting a role in modulating C. elegansphysiology.
- Huijie Liu
- , Xueren Wang
- & Ge Shan
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| Open AccessEvolution of a tissue-specific silencer underlies divergence in the expression of pax2 and pax8 paralogues
Gene paralogues generated during whole-genome duplication events often display distinct tissue expression. In this study, the distinct expression of thepax2 and pax8 paralogues is shown to be governed by the addition of a silencer in the proximal promoter of pax8that limits its tissue expression.
- Haruki Ochi
- , Tomoko Tamai
- & Hajime Ogino
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Transient activation of specific neurons in mice by selective expression of the capsaicin receptor
The ability to spatially and temporally control excitation of neuronsin vivo is an invaluable tool. By expressing the TRPV1 receptor in specific neuronal populations, Güler et al. have developed a rapid and noninvasive method to stimulate neuronal activity by the simple administration of capsaicin.
- Ali D. Güler
- , Aundrea Rainwater
- & Richard D. Palmiter
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| Open AccessDynamics of anterior–posterior axis formation in the developing mouse embryo
Detailed analysis of axis development in mouse embryo has been limited. Morriset al. developed an in vitroculture technique that enables the real-time observation of an anterior visceral endoderm formation and show that cell marker asymmetry within the AVE subdomain dictates the direction of the AVE migration.
- Samantha A. Morris
- , Seema Grewal
- & Magdalena Zernicka-Goetz
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gp96 expression in neutrophils is critical for the onset of Escherichia coli K1 (RS218) meningitis
E. coliK1 can elude the innate immune system and cause neonatal meningitis. This study shows thatE. coli K1 enters polymorphonuclear leukocytes (PMNs) using gp96 to reduce the oxidative burst, and that PMN-depleted mice are resistant to E. coliK1 infection, suggesting that PMNs permit bacterial survival in the host.
- Rahul Mittal
- & Nemani V. Prasadarao
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Genetic dissection of axon regeneration via in vivo electroporation of adult mouse sensory neurons
Dorsal root ganglion neurons can regenerate after injury, but the mechanisms underlying axon regrowth are unclear. To address this, an electroporation transfection method is developed that can alter the gene expression of dorsal root ganglion cells in a living adult mouse, providing a tool to study axon regeneration.
- Saijilafu
- , Eun-Mi Hur
- & Feng-Quan Zhou
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Article
| Open AccessTravelling and splitting of a wave of hedgehog expression involved in spider-head segmentation
During development, waves of gene expression are required for segmentation of the body axis. In this study, repeated splitting of a wave of hedgehog gene expression is shown during segmentation of the spiderAchaearanea tepidariorum.
- Masaki Kanayama
- , Yasuko Akiyama-Oda
- & Hiroki Oda
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Critical roles for EphB and ephrin-B bidirectional signalling in retinocollicular mapping
How retinoganglion cell axons project correctly to the superior colliculus is poorly understood. Here, projections are shown to require EphB1, EphB2 and ephrin-B1 to terminate in the medial superior colliculus, while ephrin-B2 is essential for the mapping of both dorsal and ventral axons.
- Sonal Thakar
- , George Chenaux
- & Mark Henkemeyer
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Article
| Open AccessFunctional and molecular interactions between ERK and CHK2 in diffuse large B-cell lymphoma
Chk2 is a kinase that is a potential chemotherapeutic target. Here, Chk2 and the kinase ERK are shown to functionally interact, and are elevated in expression in human diffuse B-cell lymphomas. Combinatorial inhibition of the kinases was also shown to block tumour growth in anin vivomouse model.
- Bojie Dai
- , X. Frank Zhao
- & Ronald B. Gartenhaus
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A photoconvertible fluorescent reporter to track chaperone-mediated autophagy
Soluble cytosolic proteins can be degraded in lysosomes by chaperone-mediated autophagy, however, the current method to measure this process requires isolation of lysosomes. Now, a fluorescent reporter is described that can measure this type of autophagy in intact cells.
- Hiroshi Koga
- , Marta Martinez-Vicente
- & Ana Maria Cuervo
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Identification of the PGRMC1 protein complex as the putative sigma-2 receptor binding site
The sigma-2 receptor is used as a biomarker for tumour cell proliferation but its identity is unknown. Using a novel radiolabelled probe, the authors identify progesterone receptor membrane component 1, which is overexpressed in several tumour types, as the putative sigma-2 receptor.
- Jinbin Xu
- , Chenbo Zeng
- & Robert H. Mach
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| Open AccessRespiratory distress and perinatal lethality in Nedd4-2-deficient mice
In vitrostudies have suggested that the ubiquitin ligase, Nedd4-2, regulates several proteins, including the epithelial sodium channel. Here by examining Nedd4-2-deficient mice, the authors demonstrate that Nedd4-2 is essential for epithelial sodium channel regulation, fetal and postnatal lung function and animal survival.
- Natasha A. Boase
- , Grigori Y. Rychkov
- & Sharad Kumar
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| Open AccessHerpesviruses carrying a Brainbow cassette reveal replication and expression of limited numbers of incoming genomes
The replication of viral genomes in infected cells is required for successful infection. In this study, using Cre-conditional expression of multiple coloured fluorophores, the authors demonstrate that the number of viral genomes expressed and replicated in a cell is surprisingly limited.
- Oren Kobiler
- , Yaron Lipman
- & Lynn W. Enquist
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| Open AccessDynamic evolution of precise regulatory encodings creates the clustered site signature of enhancers
InDrosophila development, DNA enhancers drive gene expression in response to morphogen gradients. Here, Crocker et al. study the evolution of sequences that bind a Dorsal morphogen complex and demonstrate how evolutionary changes in threshold levels have resulted in complex site clustering of DNA elements.
- Justin Crocker
- , Nathan Potter
- & Albert Erives
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| Open AccessAncestry of motor innervation to pectoral fin and forelimb
It was previously thought that the nerves in the pectoral fin of fish came solely from the spinal cord. Here, motoneurons in ray-finned fish are shown to also originate from the hindbrain, demonstrating that innervation was from both the hindbrain and the spinal cord in ancesteral vertebrates.
- Leung-Hang Ma
- , Edwin Gilland
- & Robert Baker