Featured
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Single-molecule states link transcription factor binding to gene expression
A study uses single-molecule footprinting to measure protein occupancy at regulatory elements on individual molecules in human cells and describes how different properties of transcription factor binding contribute to gene expression.
- Benjamin R. Doughty
- , Michaela M. Hinks
- & William J. Greenleaf
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Normal breast tissues harbour rare populations of aneuploid epithelial cells
Using single-cell DNA sequencing we show that most healthy women harbour rare populations of aneuploid epithelial cells with copy number alteration events in their breast tissue that expand and accumulate with age.
- Yiyun Lin
- , Junke Wang
- & Nicholas Navin
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Article |
Spatially restricted immune and microbiota-driven adaptation of the gut
Intestinal regionalization is characterized by robust and resilient structural cell states and the intestine can adapt to environmental stress in a spatially controlled manner through crosstalk between immunity and structural cell homeostasis.
- Toufic Mayassi
- , Chenhao Li
- & Ramnik J. Xavier
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Article
| Open AccessAn integrated transcriptomic cell atlas of human neural organoids
A human neural organoid cell atlas integrating 36 single-cell transcriptomic datasets shows cell types and states and estimates transcriptomic similarity between primary and organoid counterparts, showing potential to assess organoid fidelity and facilitate protocol development.
- Zhisong He
- , Leander Dony
- & Barbara Treutlein
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Article
| Open AccessSingle-cell integration reveals metaplasia in inflammatory gut diseases
The study provides a comprehensive transcriptomic atlas of the human gastrointestinal tract across the lifespan, highlighting inflammation-induced changes in epithelial stem cells that alter mucosal architecture and promote further inflammation.
- Amanda J. Oliver
- , Ni Huang
- & Sarah A. Teichmann
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Read–write mechanisms of H2A ubiquitination by Polycomb repressive complex 1
Cryo-electron microscopy and biochemical studies elucidate the read–write mechanisms of non-canonical PRC1-containing RYBP in histone H2A lysine 119 monoubiquitination and their roles in maintaining epigenetic inheritance.
- Victoria Godínez López
- , Marco Igor Valencia-Sánchez
- & Karim-Jean Armache
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Technology Feature |
Circular logic: understanding RNA’s strangest form yet
Circular RNAs are prevalent, mysterious and fascinating, but their study requires great care.
- Amber Dance
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Article
| Open AccessIdentification and genetic dissection of convergent persister cell states
Single-cell transcriptome analyses of growth phases in Escherichia coli identify a distinct transcriptional state occupied by antibiotic-tolerant persisters in which lon and yqgE have major roles.
- Sydney B. Blattman
- , Wenyan Jiang
- & Saeed Tavazoie
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Article |
A mechanism for hypoxia-induced inflammatory cell death in cancer
We find that PTP1B and ABL1/2 reciprocally control RNF213 tyrosine phosphorylation and its oligomerization and RZ domain activation, and identify a unique PTP1B–RNF213–CYLD–SPATA2 pathway critical for the control of inflammatory cell death in hypoxic tumours.
- Abhishek Bhardwaj
- , Maria C. Panepinto
- & Benjamin G. Neel
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Postsynaptic competition between calcineurin and PKA regulates mammalian sleep–wake cycles
Calcineurin–PP1 and PKA acting at excitatory post-synapses reciprocally regulate sleep duration in mice, whereby PKA promotes wakefulness and calcineurin–PP1 promote sleep.
- Yimeng Wang
- , Siyu Cao
- & Hiroki R. Ueda
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Colibactin-driven colon cancer requires adhesin-mediated epithelial binding
The oncogenic potential of pks+ Escherichia coli depends critically on bacterial adhesion to host epithelial cells mediated by the type 1 pilus adhesin FimH and the F9 pilus adhesin FmlH.
- Maude Jans
- , Magdalena Kolata
- & Lars Vereecke
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News Feature |
What’s so special about the human brain? A graphical guide
Torrents of data from cell atlases, brain organoids and other methods are finally delivering answers to an age-old question.
- Kerri Smith
- & Nik Spencer
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News |
New species of tardigrade reveals secrets of radiation-resisting powers
Knowing the genes responsible for water bears’ radiation tolerance could lead to diverse applications, from cancer treatment to space exploration.
- Miryam Naddaf
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News |
DNA stores data in bits after epigenetic upgrade
‘Bricks’ of DNA, some of which have chemical tags, could one day be an alternative to storing information electronically.
- Heidi Ledford
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Article |
Nuclear release of eIF1 restricts start-codon selection during mitosis
Transcriptome-wide profiling studies in mammalian cells show that the stringency of start-codon selection is increased during mitosis, and that this is regulated by nuclear eIF1 to preserve mitotic arrest physiology.
- Jimmy Ly
- , Kehui Xiang
- & Iain M. Cheeseman
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Chromatin remodelling drives immune cell–fibroblast communication in heart failure
Conditional deletion of the transcriptional co-activator Brd4 in infiltrating Cx3cr1+ mouse macrophages ameliorates heart failure and substantially reduces fibroblast activation.
- Michael Alexanian
- , Arun Padmanabhan
- & Deepak Srivastava
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Targeting immune–fibroblast cell communication in heart failure
A fibroblast lineage marked by FAP gives rise to POSTN-expressing fibroblasts resembling matrifibrocytes and IL-1β regulates FAP/POSTN fibroblast specification by directly signalling to cardiac fibroblasts, highlighting a role for immunomodulators in targeting cardiac fibrosis.
- Junedh M. Amrute
- , Xin Luo
- & Kory J. Lavine
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Article
| Open AccessTemporally distinct 3D multi-omic dynamics in the developing human brain
Using a single-nucleus multi-omics approach, a study jointly profiles the reorganization of the epigenome and the three-dimensional chromatin conformation during the development of the human hippocampus and prefrontal cortex.
- Matthew G. Heffel
- , Jingtian Zhou
- & Chongyuan Luo
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Rapid homologue juxtaposition during meiotic chromosome pairing
Homologue juxtaposition during meiosis is examined in real time by imaging of tagged chromosomal loci at high resolution in budding yeast, showing that corresponding loci come together and complete pairing in a very short time.
- Tadasu Nozaki
- , Beth Weiner
- & Nancy Kleckner
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Article
| Open AccessRNA m5C oxidation by TET2 regulates chromatin state and leukaemogenesis
Chromatin-associated retrotransposon RNA 5-methylcytosine can be recognized by the methyl-CpG-binding-domain protein MBD6, which guides deubiquitination of nearby monoubiquitinated Lys119 of histone H2A to promote an open chromatin state in TET2-deficient cells.
- Zhongyu Zou
- , Xiaoyang Dou
- & Chuan He
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Technology Feature |
Twenty years of Addgene
As the non-profit plasmid repository celebrates two decades, Nature looks at the stories behind some of its most requested DNA tools.
- Ariana Remmel
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Article |
Structural basis of archaeal FttA-dependent transcription termination
Cryo-electron microscopy structures of the Thermococcus kodakarensis transcription pre-termination complex suggest a mechanism by which the archaeal termination factor FttA applies mechanical force to a transcription elongation complex to trigger termination, and reveal similarities in factor-dependent termination in bacteria, archaea, and eukaryotes.
- Linlin You
- , Chengyuan Wang
- & Richard H. Ebright
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News Feature |
What is a cell type, really? The quest to categorize life’s myriad forms
Scientists have more information than ever on how cells differ — but they still resist easy grouping.
- Amber Dance
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Article
| Open AccessTwo-factor authentication underpins the precision of the piRNA pathway
In male mouse germline development, the precise DNA methylation of young, active transposons requires a two-step process in which SPIN1 and SPOCD1 mark young LINE1 elements before the piRNA pathway triggers DNA methylation.
- Madeleine Dias Mirandela
- , Ansgar Zoch
- & Dónal O’Carroll
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Technology Feature |
Red light, green light: flickering fluorophores reveal biochemistry in cells
A mysterious afterglow in a pandemic side project leads to a new method for observing proteins that interact in living cells.
- Alla Katsnelson
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Article
| Open AccessStructure of the human TIP60-C histone exchange and acetyltransferase complex
The structure of human TIP60-C uncovers a molecular machine that modifies and exchanges histones in the nucleosome, illustrating how vertebrates merge these activities, which are carried out by two independent assemblies in yeast.
- Changqing Li
- , Ekaterina Smirnova
- & Adam Ben-Shem
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Article
| Open AccessMechanism of BRCA1–BARD1 function in DNA end resection and DNA protection
BRCA1–BARD1 directly promotes double-strand break repair by stimulating long-range DNA end resection pathways.
- Ilaria Ceppi
- , Maria Rosaria Dello Stritto
- & Petr Cejka
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Promotion of DNA end resection by BRCA1–BARD1 in homologous recombination
Using highly purified protein factors, we provide evidence that BRCA1–BARD1 physically interacts with EXO1, BLM and WRN and upregulates the activity of all three resection pathways.
- Sameer Salunkhe
- , James M. Daley
- & Patrick Sung
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Article
| Open AccessHeteromeric amyloid filaments of ANXA11 and TDP-43 in FTLD-TDP type C
Using cryo-electron microscopy, heteromeric amyloid filaments composed of TDP-43 and ANXA11 in the brains of patients with frontotemporal lobar degeneration type C are discovered.
- Diana Arseni
- , Takashi Nonaka
- & Benjamin Ryskeldi-Falcon
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Perspective |
Deciphering the impact of genomic variation on function
The Impact of Genomic Variation on Function Consortium is combining single-cell mapping, genomic perturbations and predictive modelling to investigate relationships between human genomic variation, genome function and phenotypes and will provide an open resource to the community.
- Jesse M. Engreitz
- , Heather A. Lawson
- & Ella K. Samer
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Article
| Open AccessDNA methylation controls stemness of astrocytes in health and ischaemia
Single-cell analysis of the transcriptome, chromatin accessibility and methylome of adult neural stem cells and astrocytes demonstrates that stemness is driven by methylation profiles distinct from those of astrocytes.
- Lukas P. M. Kremer
- , Santiago Cerrizuela
- & Ana Martin-Villalba
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The genomes of all lungfish inform on genome expansion and tetrapod evolution
We find that massive genome expansion seems to be related to a reduction of PIWI-interacting RNAs and C2H2 zinc-finger and KRAB-domain protein genes that suppress transposable element expansion, and lungfish chromosomes still conservatively reflect the ur-tetrapod karyotype.
- Manfred Schartl
- , Joost M. Woltering
- & Axel Meyer
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Remodelling of the translatome controls diet and its impact on tumorigenesis
During fasting, hepatocytes selectively remodel the translatome while global translation is downregulated, showing a new signalling property of fatty acids and that, on a ketogenic diet, treatment with eFT508 (also known as tomivosertib; a P-eIF4E inhibitor) restrains pancreatic tumour growth.
- Haojun Yang
- , Vincenzo Andrea Zingaro
- & Davide Ruggero
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News & Views |
Rare developmental disorder caused by variants in a small RNA gene
Genetic variants in RNU4-2, a gene in a part of the genome not usually in the spotlight, have been identified as the cause of a developmental disorder in a large number of individuals who previously lacked a diagnosis.
- Henrike Heyne
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Research Briefing |
How migrating cells define their back to move forward
Migrating cells must determine where to form a front end and a back end. A gradient in contact sites between the cell membrane and an organelle called the endoplasmic reticulum (ER) is generated by a gradient of ER curvature and is required to guide and control migration speed.
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Book Review |
Never underestimate RNA: how a molecule went from bit player to star of the show
An insider’s story of the discoveries that revealed the dazzling abilities of RNA, and the therapeutic possibilities that emerged.
- John Mattick
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Article
| Open AccessFANCD2–FANCI surveys DNA and recognizes double- to single-stranded junctions
FANCD2–FANCI is a sliding clamp that diffuses on double-stranded DNA but stalls when it reaches a single-stranded gap, providing a unified molecular mechanism that reconciles the roles of FANCD2–FANCI in the recognition and protection of stalled replication forks.
- Pablo Alcón
- , Artur P. Kaczmarczyk
- & Lori A. Passmore
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SMYD5 methylation of rpL40 links ribosomal output to gastric cancer
The lysine methyltransferase SMYD5 and its newly identified substrate ribosomal protein L40 are implicated in the progression of gastric adenocarcinoma, and ablation of SMYD5 prevents metastatic disease in mouse models of this cancer.
- Juhyung Park
- , Jibo Wu
- & Pawel K. Mazur
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Article
| Open AccessSymbolic recording of signalling and cis-regulatory element activity to DNA
Enhancer-driven genomic recording of transcriptional activity in multiplex (ENGRAM) is used for multiplex recording of the cell-type-specific activities of dozens to hundreds of cis-regulatory elements with high fidelity, sensitivity and reproducibility.
- Wei Chen
- , Junhong Choi
- & Jay Shendure
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Article |
Identification of plant transcriptional activation domains
A high-throughput yeast-based assay is used to identify more than 1,500 activation domains (ADs) in Arabidopsis transcription factors, and a deep learning approach applied to this dataset can predict AD activity on the basis of sequence features.
- Nicholas Morffy
- , Lisa Van den Broeck
- & Lucia C. Strader
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Article
| Open AccessPosition-dependent function of human sequence-specific transcription factors
The effect of transcription factor binding on transcription initiation is dependent on the position of the transcription factor binding site.
- Sascha H. Duttke
- , Carlos Guzman
- & Christopher Benner
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Article
| Open AccessSources of gene expression variation in a globally diverse human cohort
A new open-access RNA sequencing dataset, MAGE, of 731 individuals across geographically diverse human populations provides a valuable resource to study genetic diversity and evolution and expands the capacity to identify new genetic associations.
- Dylan J. Taylor
- , Surya B. Chhetri
- & Rajiv C. McCoy
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Article
| Open AccessDe novo variants in the RNU4-2 snRNA cause a frequent neurodevelopmental syndrome
The non-coding RNA RNU4-2, which is highly expressed in the developing human brain, is identified as a syndromic neurodevelopmental disorder gene, and, using RNA sequencing, 5′ splice-site use is shown to be systematically disrupted in individuals with RNU4-2 variants.
- Yuyang Chen
- , Ruebena Dawes
- & Nicola Whiffin
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News |
How Denisovans thrived on top of the world: mysterious ancient humans’ survival secrets revealed
The cave-dwelling group hunted animals such as hyenas and hares to sustain themselves in harsh environments.
- Ewen Callaway
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Article |
Targeting pericentric non-consecutive motifs for heterochromatin initiation
Zinc-finger proteins ZNF512 and ZNF512B are shown to target pericentric DNA through a conserved mechanism that depends on their atypical long linkers, providing insight into how constitutive heterochromatin formation is initiated across various species.
- Runze Ma
- , Yan Zhang
- & Bing Zhu
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News & Views |
Programmable RNA-guided enzymes for next-generation genome editing
RNA-guided recombinase enzymes have been discovered that herald a new chapter for genome editing — enabling the insertion, inversion or deletion of long DNA sequences at user-specified genome positions.
- Connor J. Tou
- & Benjamin P. Kleinstiver
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Article
| Open AccessBridge RNAs direct programmable recombination of target and donor DNA
A bispecific non-coding RNA expressed by the IS110 family of mobile genetic elements forms the basis of a programmable genome-editing system that enables the insertion, excision or inversion of specific target DNA sequences.
- Matthew G. Durrant
- , Nicholas T. Perry
- & Patrick D. Hsu
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Comment |
The strategy behind one of the most successful labs in the world
One UK institute has produced a dozen Nobel laureates and biomedical breakthroughs across the board. How does Cambridge’s Laboratory of Molecular Biology do it? Our study found out.
- Luka Gebel
- , Chander Velu
- & Antonio Vidal-Puig
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Article
| Open AccessStructural mechanism of bridge RNA-guided recombination
Using cryo-electron microscopy, the structural mechanism by which non-coding bridge RNA confers target and donor DNA specificity to IS110 recombinases for programmable DNA recombination is explored.
- Masahiro Hiraizumi
- , Nicholas T. Perry
- & Hiroshi Nishimasu
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