目次

Editorials

米議会の対立が続いて厳しい歳出削減が回避できないと、科学に長期的なダメージが残るだろう。

Starvation diet p.401

A severe approach to slashing US spending bodes ill for the research enterprise.

doi: 10.1038/494401b

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科学のためには、論文を読者の費用負担なく即時公開する「ゴールド」オープンアクセス化が必要だ。

Gold on hold p.401

The move towards providing full open access to research papers was undermined last week, but should prevail in the long term.

doi: 10.1038/494401a

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幅広い分野を対象としながら、新設の「生命科学ブレークスルー賞」の受賞者が狭い範囲に偏っていることは懸念される。

Prize drawback p.402

The narrow distribution of awards aimed at the broad arena of the ‘life sciences’ raises concerns.

doi: 10.1038/494402a

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News

米国の次のエネルギー省長官に、マサチューセッツ工科大学の物理学者が。

Physicist tipped for US energy post p.409

Ernest Moniz considers natural gas a bridge to clean energy.

doi: 10.1038/494409a

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心疾患の治療指針の改訂で、コレステロールの目標値設定を見直しへ。

Cholesterol limits lose their lustre p.410

Revised guidelines for heart health are set to move away from target-based approach.

doi: 10.1038/494410a

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象牙の鑑定による不正取引の追跡が、ゾウの保護のカギに。

Tusk tracking will tackle illegal trade p.411

Forensic testing of seized ivory could track down poachers.

doi: 10.1038/494411a

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理化学研究所が、iPS細胞の初めての臨床試験へ。

Stem cells cruise to clinic p.413

Japanese study of induced pluripotent stem cells aims to demonstrate safety in humans.

doi: 10.1038/494413a

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米政府が、公的予算で行った科学研究のオープンアクセス化を義務付けへ。

US science to be open to all p.414

Government mandates that taxpayer-funded research be freely available within 12 months.

doi: 10.1038/494414a

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自然に生じる環状RNAが遺伝子発現を変化させていることがわかり、遺伝学界に驚きが。

Circular RNAs throw genetics for a loop p.415

RNA ‘sponges’ mop up sequences that curb gene expression.

doi: 10.1038/494415a

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News Features

表紙:オームのパズル

Big biology: The 'omes puzzle p.416

ゲノム(genome)に始まり、今では「オーム(ome)」が付く言葉がいくつも存在するが、存在意義のあるものばかりなのだろうか。

doi: 10.1038/494416a

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政策:科学にとって頼りになる男

America’s research adviser: Science's go-to guy p.420

ロッキード・マーチン社の元最高経営責任者オーガスティン氏は科学者ではないが、政治家からも研究者からも信頼され、米国の科学に大きな影響力を持っている。

doi: 10.1038/494420a

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News & Views

宇宙物理学:回転するブラックホール

Astrophysics: Black holes in a spin p.432

大質量ブラックホールが存在する銀河からのX線放射パターンが何を意味するのかについては議論が続いてきた。NASAのNuSTAR宇宙望遠鏡からのデータは、少なくともこのような銀河の1つに関しては、問題の解決につながりそうだ。

doi: 10.1038/494432a

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ウイルス学:宿主の防御装備を乗っ取るファージ

Virology: Phages hijack a host's defence p.433

一部のウイルスがCRISPR/Cas系と呼ばれている防御機構を使うという発見は、ウイルスとその感染相手である細菌の間で進化してきた「しっぺ返し」を示す、見事な例である。

doi: 10.1038/494433a

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ことばの科学:リズムに合わせる

Speech science: Tuned to the rhythm p.434

マカクザルが、唇を鳴らしているサルの顔のコンピューターアニメーションを見たときの反応は、ヒトの発話を特徴付ける顎、舌と唇の振動が、霊長類の顔の表情のリズミカルな動きから進化した可能性を示唆している。

doi: 10.1038/494434a

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環境科学:窒素の来るべき形態

Environmental science: The shape of nitrogen to come p.435

中国では、窒素循環に人間活動が非常に大きな影響を与えていることが分析から明らかになった。この知見は、地球資源の1人当たりの使用が全球的に増大していることと合わせて、先進国の消費パターンの再検討を求めている。

doi: 10.1038/nature11954

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栄養:居候が敵に転じると

Nutrition: When guests turn hostile p.437

どんなに栄養豊富な食餌であっても、その影響は宿主に寄生している腸内細菌叢にきわめて大きく依存している。重度の栄養不良の治療に抗生物質を使えば、このような細菌叢の構成に影響を与えて栄養素をもっとうまく使えるようになるかもしれない。

doi: 10.1038/494437a

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寄生虫学:幹細胞を介しての若返り

Parasitology: Rejuvenation through stem cells p.438

住血吸虫は成体幹細胞を持っていることがわかった。これは住血吸虫がヒトの体内に長期にわたって住みつくことの説明となる可能性がある。細胞が産生するタンパク質の1つを標的とすれば、住血吸虫の防御機構に損傷を与えられるかもしれない。

doi: 10.1038/nature11953

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がん:ストレスが染色体を混ぜ合わす

Cancer: Stress mixes chromosomes p.439

細胞分裂の際の染色体の分離に起こった誤りは、腫瘍の進化に重要な役割を持つ可能性がある。こういった過誤の原因となる一般的な遺伝的欠陥がやっと見つかったが、それによってもたらされた意外な進展は関心を集めそうだ。

doi: 10.1038/494439a

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Article

構造生物学:完全な呼吸鎖複合体Iの結晶構造

Crystal structure of the entire respiratory complex I p.443

The atomic-resolution structure of the entire respiratory complex I is reported, with the resolution high enough to map out the locations and orientations of nearly all amino-acid side chains—some of which link to human neurodegenerative diseases—and reveals which amino-acid interactions take place at the hydrophilic domain–membrane domain interface.

doi: 10.1038/nature11871

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Letters

宇宙:NGC 1365の中心部に位置する急速に回転する超大質量ブラックホール

A rapidly spinning supermassive black hole at the centre of NGC 1365 p.449

Broad X-ray emission lines from neutral and partially ionized iron observed in active galaxies have been interpreted as fluorescence produced by the reflection of hard X-rays off the inner edge of an accretion disk. In this model, line broadening and distortion result from rapid rotation and relativistic effects near the black hole, the line shape being sensitive to its spin. Alternative models in which the distortions result from absorption by intervening structures provide an equally good description of the data, and there has been no general agreement on which is correct. Recent claims that the black hole (2 × 106 solar masses) at the centre of the galaxy NGC 1365 is rotating at close to its maximum possible speed rest on the assumption of relativistic reflection. Here we report X-ray observations of NGC 1365 that reveal the relativistic disk features through broadened Fe-line emission and an associated Compton scattering excess of 10–30 kiloelectronvolts. Using temporal and spectral analyses, we disentangle continuum changes due to time-variable absorption from reflection, which we find arises from a region within 2.5 gravitational radii of the rapidly spinning black hole. Absorption-dominated models that do not include relativistic disk reflection can be ruled out both statistically and on physical grounds.

doi: 10.1038/nature11938

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宇宙:水星よりも小さい系外惑星

A sub-Mercury-sized exoplanet p.452

Since the discovery of the first exoplanets, it has been known that other planetary systems can look quite unlike our own. Until fairly recently, we have been able to probe only the upper range of the planet size distribution, and, since last year, to detect planets that are the size of Earth or somewhat smaller. Hitherto, no planets have been found that are smaller than those we see in the Solar System. Here we report a planet significantly smaller than Mercury. This tiny planet is the innermost of three that orbit the Sun-like host star, which we have designated Kepler-37. Owing to its extremely small size, similar to that of the Moon, and highly irradiated surface, the planet, Kepler-37b, is probably rocky with no atmosphere or water, similar to Mercury.

doi: 10.1038/nature11914

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材料:単一の膜貫通窒化ホウ素ナノチューブにおいて測定された巨大な浸透エネルギー変換

Giant osmotic energy conversion measured in a single transmembrane boron nitride nanotube p.455

New models of fluid transport are expected to emerge from the confinement of liquids at the nanoscale, with potential applications in ultrafiltration, desalination and energy conversion. Nevertheless, advancing our fundamental understanding of fluid transport on the smallest scales requires mass and ion dynamics to be ultimately characterized across an individual channel to avoid averaging over many pores. A major challenge for nanofluidics thus lies in building distinct and well-controlled nanochannels, amenable to the systematic exploration of their properties. Here we describe the fabrication and use of a hierarchical nanofluidic device made of a boron nitride nanotube that pierces an ultrathin membrane and connects two fluid reservoirs. Such a transmembrane geometry allows the detailed study of fluidic transport through a single nanotube under diverse forces, including electric fields, pressure drops and chemical gradients. Using this device, we discover very large, osmotically induced electric currents generated by salinity gradients, exceeding by two orders of magnitude their pressure-driven counterpart. We show that this result originates in the anomalously high surface charge carried by the nanotube’s internal surface in water at large pH, which we independently quantify in conductance measurements. The nano-assembly route using nanostructures as building blocks opens the way to studying fluid, ionic and molecule transport on the nanoscale, and may lead to biomimetic functionalities. Our results furthermore suggest that boron nitride nanotubes could be used as membranes for osmotic power harvesting under salinity gradients.

doi: 10.1038/nature11876

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環境:中国全土にわたる窒素蓄積量の増加

Enhanced nitrogen deposition over China p.459

China is experiencing intense air pollution caused in large part by anthropogenic emissions of reactive nitrogen. These emissions result in the deposition of atmospheric nitrogen (N) in terrestrial and aquatic ecosystems, with implications for human and ecosystem health, greenhouse gas balances and biological diversity. However, information on the magnitude and environmental impact of N deposition in China is limited. Here we use nationwide data sets on bulk N deposition, plant foliar N and crop N uptake (from long-term unfertilized soils) to evaluate N deposition dynamics and their effect on ecosystems across China between 1980 and 2010. We find that the average annual bulk deposition of N increased by approximately 8 kilograms of nitrogen per hectare (P < 0.001) between the 1980s (13.2 kilograms of nitrogen per hectare) and the 2000s (21.1 kilograms of nitrogen per hectare). Nitrogen deposition rates in the industrialized and agriculturally intensified regions of China are as high as the peak levels of deposition in northwestern Europe in the 1980s, before the introduction of mitigation measures. Nitrogen from ammonium (NH4+) is the dominant form of N in bulk deposition, but the rate of increase is largest for deposition of N from nitrate (NO3), in agreement with decreased ratios of NH3 to NOx emissions since 1980. We also find that the impact of N deposition on Chinese ecosystems includes significantly increased plant foliar N concentrations in natural and semi-natural (that is, non-agricultural) ecosystems and increased crop N uptake from long-term-unfertilized croplands. China and other economies are facing a continuing challenge to reduce emissions of reactive nitrogen, N deposition and their negative effects on human health and the environment.

doi: 10.1038/nature11917

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進化:絶滅からの進化的救済は低速の環境変化が条件である

Evolutionary rescue from extinction is contingent on a lower rate of environmental change p.463

The extinction rate of populations is predicted to rise under increasing rates of environmental change. If a population experiencing increasingly stressful conditions lacks appropriate phenotypic plasticity or access to more suitable habitats, then genetic change may be the only way to avoid extinction. Evolutionary rescue from extinction occurs when natural selection enriches a population for more stress-tolerant genetic variants. Some experimental studies have shown that lower rates of environmental change lead to more adapted populations or fewer extinctions. However, there has been little focus on the genetic changes that underlie evolutionary rescue. Here we demonstrate that some evolutionary trajectories are contingent on a lower rate of environmental change. We allowed hundreds of populations of Escherichia coli to evolve under variable rates of increase in concentration of the antibiotic rifampicin. We then genetically engineered all combinations of mutations from isolates evolved under lower rates of environmental change. By assessing fitness of these engineered strains across a range of drug concentrations, we show that certain genotypes are evolutionarily inaccessible under rapid environmental change. Rapidly deteriorating environments not only limit mutational opportunities by lowering population size, but they can also eliminate sets of mutations as evolutionary options. As anthropogenic activities are leading to environmental change at unprecedented rapidity, it is critical to understand how the rate of environmental change affects both demographic and genetic underpinnings of evolutionary rescue.

doi: 10.1038/nature11879

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進化:フキシャンフィア類の特殊化した付属肢と初期の真節足動物の頭部の構成

Specialized appendages in fuxianhuiids and the head organization of early euarthropods p.468

The organization of the head provides critical data for resolving the phylogenetic relationships and evolutionary history of extinct and extant euarthropods. The early Cambrian-period fuxianhuiids are regarded as basal representatives of stem-group Euarthropoda, and their anterior morphology therefore offers key insights for reconstructing the ancestral condition of the euarthropod head. However, the paired post-antennal structures in Fuxianhuia protensa remain controversial; they have been interpreted as both ‘great appendages’ and as gut diverticulae. Here we describe Chengjiangocaris kunmingensis sp. nov. and Fuxianhuia xiaoshibaensis sp. nov. from a new early Cambrian (Stage 3) fossil Lagerstätte in Yunnan, China. Numerous specimens of both species show a unique ‘taphonomic dissection’ of the anterodorsal head shield, revealing the cephalic organization in detail. We demonstrate the presence of a pair of specialized post-antennal appendages (SPAs) in the fuxianhuiid head, which attach at either side of the posteriorly directed mouth, behind the hypostome. Preserved functional articulations indicate a well-defined but restricted range of limb movement, suggestive of a simple type of sweep feeding. The organization of the SPAs in fuxianhuiids is incompatible with the (deutocerebral) anterior raptorial appendages of megacheirans, and argue against the presence of protocerebral limbs in the fuxianhuiids. The positions of the fuxianhuiid antennae and SPAs indicate that they are segmentally homologous to the deutocerebral and tritocerebral appendages of crown-group Euarthropoda respectively. These findings indicate that antenniform deutocerebral appendages with many podomeres are a plesiomorphic feature of the ancestral euarthropod head.

doi: 10.1038/nature11874

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神経科学:高濃度の塩は嫌悪味覚経路を動員する

High salt recruits aversive taste pathways p.472

In the tongue, distinct classes of taste receptor cells detect the five basic tastes; sweet, sour, bitter, sodium salt and umami. Among these qualities, bitter and sour stimuli are innately aversive, whereas sweet and umami are appetitive and generally attractive to animals. By contrast, salty taste is unique in that increasing salt concentration fundamentally transforms an innately appetitive stimulus into a powerfully aversive one. This appetitive–aversive balance helps to maintain appropriate salt consumption, and represents an important part of fluid and electrolyte homeostasis. We have shown previously that the appetitive responses to NaCl are mediated by taste receptor cells expressing the epithelial sodium channel, ENaC, but the cellular substrate for salt aversion was unknown. Here we examine the cellular and molecular basis for the rejection of high concentrations of salts. We show that high salt recruits the two primary aversive taste pathways by activating the sour- and bitter-taste-sensing cells. We also demonstrate that genetic silencing of these pathways abolishes behavioural aversion to concentrated salt, without impairing salt attraction. Notably, mice devoid of salt-aversion pathways show unimpeded, continuous attraction even to very high concentrations of NaCl. We propose that the ‘co-opting’ of sour and bitter neural pathways evolved as a means to ensure that high levels of salt reliably trigger robust behavioural rejection, thus preventing its potentially detrimental effects on health.

doi: 10.1038/nature11905

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微生物学:ヒト寄生虫マンソン住血吸虫の成体体性幹細胞

Adult somatic stem cells in the human parasite Schistosoma mansoni p.476

Schistosomiasis is among the most prevalent human parasitic diseases, affecting more than 200 million people worldwide. The aetiological agents of this disease are trematode flatworms (Schistosoma) that live and lay eggs within the vasculature of the host. These eggs lodge in host tissues, causing inflammatory responses that are the primary cause of morbidity. Because these parasites can live and reproduce within human hosts for decades, elucidating the mechanisms that promote their longevity is of fundamental importance. Although adult pluripotent stem cells, called neoblasts, drive long-term homeostatic tissue maintenance in long-lived free-living flatworms (for example, planarians), and neoblast-like cells have been described in some parasitic tapeworms, little is known about whether similar cell types exist in any trematode species. Here we describe a population of neoblast-like cells in the trematode Schistosoma mansoni. These cells resemble planarian neoblasts morphologically and share their ability to proliferate and differentiate into derivatives of multiple germ layers. Capitalizing on available genomic resources and RNA-seq-based gene expression profiling, we find that these schistosome neoblast-like cells express a fibroblast growth factor receptor orthologue. Using RNA interference we demonstrate that this gene is required for the maintenance of these neoblast-like cells. Our observations indicate that adaptation of developmental strategies shared by free-living ancestors to modern-day schistosomes probably contributed to the success of these animals as long-lived obligate parasites. We expect that future studies deciphering the function of these neoblast-like cells will have important implications for understanding the biology of these devastating parasites.

doi: 10.1038/nature11924

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細胞:固定処理した細胞から抽出した動態によって明らかになった、細胞成長と細胞周期をつなぐフィードバック

Dynamics extracted from fixed cells reveal feedback linking cell growth to cell cycle p.480

Biologists have long been concerned about what constrains variation in cell size, but progress in this field has been slow and stymied by experimental limitations. Here we describe a new method, ergodic rate analysis (ERA), that uses single-cell measurements of fixed steady-state populations to accurately infer the rates of molecular events, including rates of cell growth. ERA exploits the fact that the number of cells in a particular state is related to the average transit time through that state. With this method, it is possible to calculate full time trajectories of any feature that can be labelled in fixed cells, for example levels of phosphoproteins or total cellular mass. Using ERA we find evidence for a size-discriminatory process at the G1/S transition that acts to decrease cell-to-cell size variation.

doi: 10.1038/nature11897

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医学:非典型的プロテインキナーゼC ι/λによるGLIの活性化が、基底細胞がんの成長を調節する

GLI activation by atypical protein kinase C ι/λ regulates the growth of basal cell carcinomas p.484

Growth of basal cell carcinomas (BCCs) requires high levels of hedgehog (HH) signalling through the transcription factor GLI. Although inhibitors of membrane protein smoothened (SMO) effectively suppress HH signalling, early tumour resistance illustrates the need for additional downstream targets for therapy. Here we identify atypical protein kinase C ι/λ (aPKC-ι/λ) as a novel GLI regulator in mammals. aPKC-ι/λ and its polarity signalling partners co-localize at the centrosome and form a complex with missing-in-metastasis (MIM), a scaffolding protein that potentiates HH signalling. Genetic or pharmacological loss of aPKC-ι/λ function blocks HH signalling and proliferation of BCC cells. Prkci is a HH target gene that forms a positive feedback loop with GLI and exists at increased levels in BCCs. Genome-wide transcriptional profiling shows that aPKC-ι/λ and SMO control the expression of similar genes in tumour cells. aPKC-ι/λ functions downstream of SMO to phosphorylate and activate GLI1, resulting in maximal DNA binding and transcriptional activation. Activated aPKC-ι/λ is upregulated in SMO-inhibitor-resistant tumours and targeting aPKC-ι/λ suppresses signalling and growth of resistant BCC cell lines. These results demonstrate that aPKC-ι/λ is critical for HH-dependent processes and implicates aPKC-ι/λ as a new, tumour-selective therapeutic target for the treatment of SMO-inhibitor-resistant cancers.

doi: 10.1038/nature11889

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微生物学:バクテリオファージは、宿主の自然免疫を回避するために自身のCRISPR/Cas適応応答をコードしている

A bacteriophage encodes its own CRISPR/Cas adaptive response to evade host innate immunity p.489

Bacteriophages (or phages) are the most abundant biological entities on earth, and are estimated to outnumber their bacterial prey by tenfold. The constant threat of phage predation has led to the evolution of a broad range of bacterial immunity mechanisms that in turn result in the evolution of diverse phage immune evasion strategies, leading to a dynamic co-evolutionary arms race. Although bacterial innate immune mechanisms against phage abound, the only documented bacterial adaptive immune system is the CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins) system, which provides sequence-specific protection from invading nucleic acids, including phage. Here we show a remarkable turn of events, in which a phage-encoded CRISPR/Cas system is used to counteract a phage inhibitory chromosomal island of the bacterial host. A successful lytic infection by the phage is dependent on sequence identity between CRISPR spacers and the target chromosomal island. In the absence of such targeting, the phage-encoded CRISPR/Cas system can acquire new spacers to evolve rapidly and ensure effective targeting of the chromosomal island to restore phage replication.

doi: 10.1038/nature11927

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医学:複製ストレスは、がんにおける構造的および数的な染色体不安定性に関連する

Replication stress links structural and numerical cancer chromosomal instability p.492

Cancer chromosomal instability (CIN) results in an increased rate of change of chromosome number and structure and generates intratumour heterogeneity. CIN is observed in most solid tumours and is associated with both poor prognosis and drug resistance. Understanding a mechanistic basis for CIN is therefore paramount. Here we find evidence for impaired replication fork progression and increased DNA replication stress in CIN+ colorectal cancer (CRC) cells relative to CIN CRC cells, with structural chromosome abnormalities precipitating chromosome missegregation in mitosis. We identify three new CIN-suppressor genes (PIGN (also known as MCD4), MEX3C (RKHD2) and ZNF516 (KIAA0222)) encoded on chromosome 18q that are subject to frequent copy number loss in CIN+ CRC. Chromosome 18q loss was temporally associated with aneuploidy onset at the adenoma–carcinoma transition. CIN-suppressor gene silencing leads to DNA replication stress, structural chromosome abnormalities and chromosome missegregation. Supplementing cells with nucleosides, to alleviate replication-associated damage, reduces the frequency of chromosome segregation errors after CIN-suppressor gene silencing, and attenuates segregation errors and DNA damage in CIN+ cells. These data implicate a central role for replication stress in the generation of structural and numerical CIN, which may inform new therapeutic approaches to limit intratumour heterogeneity.

doi: 10.1038/nature11935

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分子生物学:活性化RNAはメディエーターと会合してクロマチンの構造化と転写を促進する

Activating RNAs associate with Mediator to enhance chromatin architecture and transcription p.497

Recent advances in genomic research have revealed the existence of a large number of transcripts devoid of protein-coding potential in multiple organisms. Although the functional role for long non-coding RNAs (lncRNAs) has been best defined in epigenetic phenomena such as X-chromosome inactivation and imprinting, different classes of lncRNAs may have varied biological functions. We and others have identified a class of lncRNAs, termed ncRNA-activating (ncRNA-a), that function to activate their neighbouring genes using a cis-mediated mechanism. To define the precise mode by which such enhancer-like RNAs function, we depleted factors with known roles in transcriptional activation and assessed their role in RNA-dependent activation. Here we report that depletion of the components of the co-activator complex, Mediator, specifically and potently diminished the ncRNA-induced activation of transcription in a heterologous reporter assay using human HEK293 cells. In vivo, Mediator is recruited to ncRNA-a target genes and regulates their expression. We show that ncRNA-a interact with Mediator to regulate its chromatin localization and kinase activity towards histone H3 serine 10. The Mediator complex harbouring disease- displays diminished ability to associate with activating ncRNAs. Chromosome conformation capture confirmed the presence of DNA looping between the ncRNA-a loci and its targets. Importantly, depletion of Mediator subunits or ncRNA-a reduced the chromatin looping between the two loci. Our results identify the human Mediator complex as the transducer of activating ncRNAs and highlight the importance of Mediator and activating ncRNA association in human disease.

doi: 10.1038/nature11884

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細胞:TRF2を介した染色体末端保護の2段階機構

A two-step mechanism for TRF2-mediated chromosome-end protection p.502

Mammalian telomeres repress DNA-damage activation at natural chromosome ends by recruiting specific inhibitors of the DNA-damage machinery that form a protective complex termed shelterin. Within this complex, TRF2 (also known as TERF2) has a crucial role in end protection through the suppression of ATM activation and the formation of end-to-end chromosome fusions. Here we address the molecular properties of TRF2 that are both necessary and sufficient to protect chromosome ends in mouse embryonic fibroblasts. Our data support a two-step mechanism for TRF2-mediated end protection. First, the dimerization domain of TRF2 is required to inhibit ATM activation, the key initial step involved in the activation of a DNA-damage response (DDR). Next, TRF2 independently suppresses the propagation of DNA-damage signalling downstream of ATM activation. This novel modulation of the DDR at telomeres occurs at the level of the E3 ubiquitin ligase RNF168 (ref. 3). Inhibition of RNF168 at telomeres involves the deubiquitinating enzyme BRCC3 and the ubiquitin ligase UBR5, and is sufficient to suppress chromosome end-to-end fusions. This two-step mechanism for TRF2-mediated end protection helps to explain the apparent paradox of frequent localization of DDR proteins at functional telomeres without concurrent induction of detrimental DNA-repair activities.

doi: 10.1038/nature11873

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