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| Open AccessSeeding the meiotic DNA break machinery and initiating recombination on chromosome axes
Meiotic cells deliberately break their DNA to allow chromosomes to swap genetic material. Here, authors reveal genetically separable pathways controlling the seeding and growth of chromosome-bound protein condensates responsible for DNA breaks.
- Ihsan Dereli
- , Vladyslav Telychko
- & Attila Tóth
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Article
| Open AccessPARP2 promotes Break Induced Replication-mediated telomere fragility in response to replication stress
Here the authors show that PARP2 drives telomere fragility by orchestrating the Break-induced replication (BIR) pathway. This promotes DNA end resection and DNA synthesis via the regulation of POLD3.
- Daniela Muoio
- , Natalie Laspata
- & Elise Fouquerel
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Article
| Open AccessRegulation of meiotic telomere dynamics through membrane fluidity promoted by AdipoR2-ELOVL2
Meiosis is a specialized cell division for generating germ cells. The authors show that the lipid composition in the cellular membrane influences meiosis-specific chromosomal dynamics in mouse testis.
- Jingjing Zhang
- , Mario Ruiz
- & Hiroki Shibuya
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Article
| Open AccessTERRA-LSD1 phase separation promotes R-loop formation for telomere maintenance in ALT cancer cells
Here the authors show that the telomere repeat-containing RNA (TERRA) undergoes phase separation with the lysine-specific demethylase 1A (LSD1) to promote R-loop formation for homology-directed telomere DNA synthesis in the alternative lengthening of telomere (ALT) pathway.
- Meng Xu
- , Dulmi Senanayaka
- & Huaiying Zhang
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Article
| Open AccessscCircle-seq unveils the diversity and complexity of extrachromosomal circular DNAs in single cells
Extrachromosomal circular DNAs (eccDNAs) affect gene expression and tumour progression. Here, the authors report a method, scCircle-seq, for eccDNA profiling in single cells, demonstrating the stochasticity, cell type specificity, and dynamics of eccDNAs in cell lines and primary tumour samples.
- Jinxin Phaedo Chen
- , Constantin Diekmann
- & Nicola Crosetto
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Article
| Open AccessUltrastructure of macromolecular assemblies contributing to bacterial spore resistance revealed by in situ cryo-electron tomography
Bacterial endospores are among the most resilient forms of life. Here, authors reveal ultrastructural details of the spore chromosome and the multiprotein, multilayered extracellular coat, shedding light on mechanisms contributing to spore resistance.
- Elda Bauda
- , Benoit Gallet
- & Cecile Morlot
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Article
| Open AccessTigerfish designs oligonucleotide-based in situ hybridization probes targeting intervals of highly repetitive DNA at the scale of genomes
Repetitive DNA intervals play important roles in the nucleus but are difficult to study due to their reiterated nature. Tigerfish introduces a novel computational platform for the design of interval-specific in situ hybridization probes.
- Robin Aguilar
- , Conor K. Camplisson
- & Brian J. Beliveau
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| Open AccessConserved chromatin and repetitive patterns reveal slow genome evolution in frogs
Frogs are an ancient and ecologically diverse group of amphibians that include important model systems. This paper reports genome sequences of multiple frog species, revealing remarkable stability of frog chromosomes and centromeres, along with highly recombinogenic extended subtelomeres.
- Jessen V. Bredeson
- , Austin B. Mudd
- & Daniel S. Rokhsar
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Article
| Open AccessBuilding synthetic chromosomes from natural DNA
Building synthetic chromosomes from natural components is an unexplored alternative to de novo chromosome synthesis that may have many potential applications. In this paper, the authors report CReATiNG, a method for constructing synthetic chromosomes from natural components in yeast.
- Alessandro L. V. Coradini
- , Christopher Ne Ville
- & Ian M. Ehrenreich
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Article
| Open AccessZNF524 directly interacts with telomeric DNA and supports telomere integrity
ZNF524 is a newly described protein that binds to telomeres, the ends of linear chromosomes. ZNF524 promotes the presence of two members of the shelterin complex, TRF2/RAP1, at telomeres, and prevents genomic instability.
- Hanna Braun
- , Ziyan Xu
- & Dennis Kappei
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Article
| Open AccessCENP-A and CENP-B collaborate to create an open centromeric chromatin state
Centromeres are defined by the histone variant CENP-A. Using single-molecule fluorescence and cryoEM, this study shows that CENP-A and the centromeric protein CENP-B collaborate to create dynamic and open chromatin, aiding centromeric factor binding.
- Harsh Nagpal
- , Ahmad Ali-Ahmad
- & Beat Fierz
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| Open AccessDefining a core configuration for human centromeres during mitosis
The detailed 3D organization of human centromere components is unknown. Here, the authors use super-resolution microscopy to present a working model for a common core centromere structure.
- Ayantika Sen Gupta
- , Chris Seidel
- & Jennifer L. Gerton
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Article
| Open AccessBuilding a eukaryotic chromosome arm by de novo design and synthesis
In Saccharomyces cerevisiae, the left arm of chromosome XII only requires 12 genes to maintain cell viability, whereas 25 genes are needed for robust fitness. Here the authors demonstrate that the entire arm can be replaced by a neochromosome with completely artificial sequences.
- Shuangying Jiang
- , Zhouqing Luo
- & Junbiao Dai
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Article
| Open AccessGenetic separation of Brca1 functions reveal mutation-dependent Polθ vulnerabilities
Homologous recombination (HR) gene mutations are thought to be synthetic lethal with DNA polymerase theta (Polθ) inhibition. Here, the authors reveal that Polθ addiction is determined by the functional impact of gene mutations on DNA end resection activity.
- John J. Krais
- , David J. Glass
- & Neil Johnson
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Article
| Open AccessUnzipped chromosome-level genomes reveal allopolyploid nematode origin pattern as unreduced gamete hybridization
The occurrence and consequences of polyploidization in clonally reproducing animals is unclear. Here, the authors generate 4 polyploid Meloidogyne genomes, identifying a telomeric element, resolving genome structures and extensive chromosome fusion events, and revealing origin patterns.
- Dadong Dai
- , Chuanshuai Xie
- & Ming Sun
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Article
| Open Access3D chromatin interactions involving Drosophila insulators are infrequent but preferential and arise before TADs and transcription
In Drosophila, insulators may be involved in the organization of Topological Associated Domains, but the mechanism of action is a still a matter of investigation. Here the authors investigate the role of insulators in the 3D organization of the Drosophila genome by combining bioinformatics analysis and Hi-M, an imaging-based methods developed to detect the 3D positions of multiple genomic loci in single cells.
- Olivier Messina
- , Flavien Raynal
- & Marcelo Nollmann
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Article
| Open AccessStructure of native chromatin fibres revealed by Cryo-ET in situ
Here, using cryo-FIB and cryo-ET, the authors delineate the architecture of native chromatin fibers and decipher the in situ nucleosomes structure, inspiring future chromatin research.
- Zhen Hou
- , Frank Nightingale
- & Peijun Zhang
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Article
| Open AccessGlobal mapping of RNA-chromatin contacts reveals a proximity-dominated connectivity model for ncRNA-gene interactions
Many types of RNAs are associated with chromatin. Here the authors identify chromatin-bound RNAs and their binding sites in human embryonic stem cells suggesting that most chromatin-associated RNAs act proximal to their encoding loci and single RNAs are unlikely to alter gene expression.
- Charles Limouse
- , Owen K. Smith
- & Aaron F. Straight
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Article
| Open AccessConformational dynamics of cohesin/Scc2 loading complex are regulated by Smc3 acetylation and ATP binding
Cohesin loading on DNA is a highly dynamic process. Here the authors find that Smc3 acetylation blocks the reconfiguration of the Scc2/cohesin complex by preventing Scc2 from interacting with Smc3, and that ATP binding regulates the DNA clamping step by promoting the Scc2/Smc3 coiled-coil interaction.
- Aditi Kaushik
- , Thane Than
- & Bin Hu
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Article
| Open AccessNuclear lamina strain states revealed by intermolecular force biosensor
In this work, a nanobody based intermolecular strain sensor was used to follow the mechanical strain in the nuclear lamina. The results indicate that mechanical state of the nuclear lamina is not only affected by the cell contractility, but also chromatin packing.
- Brooke E. Danielsson
- , Bobin George Abraham
- & Teemu O. Ihalainen
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| Open AccessAcentrosomal spindles assemble from branching microtubule nucleation near chromosomes in Xenopus laevis egg extract
Microtubules need to be generated during cell division to build mitotic or meiotic spindles. Here, reconstitution experiments and theoretical modeling show that chromosomes alone can trigger branching microtubule nucleation.
- Bernardo Gouveia
- , Sagar U. Setru
- & Sabine Petry
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| Open AccessRio1 downregulates centromeric RNA levels to promote the timely assembly of structurally fit kinetochores
Kinetochores assemble on centromeres via histone H3 variant CENP-A and low levels of centromere transcripts (cenRNAs). Here the authors show the Rio1 kinase limits cenRNA production by reducing RNAPII accessibility and promotes cenRNA degradation by the 5’− 3’exoribonuclease Rat1.
- Ksenia Smurova
- , Michela Damizia
- & Peter De Wulf
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| Open AccessAn Aurora B-RPA signaling axis secures chromosome segregation fidelity
RPA is a master coordinator of DNA metabolism. Here, authors uncover that RPA is regulated by an Aurora B-signaling circuit that is critical for chromosome segregation in mitosis. Distinct phosphorylation of RPA70 modulates accessibility of RPA domains.
- Poonam Roshan
- , Sahiti Kuppa
- & Sofia Origanti
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Article
| Open AccessIntracellular RNA and DNA tracking by uridine-rich internal loop tagging with fluorogenic bPNA
Commonly used protein-based tools to monitor intracellular RNA and DNA can impact steric accessibility and native nucleic acid biology. Here, the authors show that fluorogenic uridine-rich internal loop tagging bPNA probes can be used to label nucleic acids in fixed and live cells.
- Yufeng Liang
- , Sydney Willey
- & Dennis Bong
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Article
| Open AccessPathway choice in the alternative telomere lengthening in neoplasia is dictated by replication fork processing mediated by EXD2’s nuclease activity
Here the authors demonstrate that remodelling of perturbed replication forks by the exonuclease EXD2 modulates pathway choice within the Alternative Lengthening of Telomeres mechanism and identify potentially clinically important synthetic lethal interactions in ALT cancer cells.
- Ronan Broderick
- , Veronica Cherdyntseva
- & Wojciech Niedzwiedz
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Article
| Open AccessDNA double-strand break end synapsis by DNA loop extrusion
DNA double-strand breaks (DSBs) occur every cell cycle and must be repaired. Here the authors combine theory and simulations to establish a likely role for loop extrusion in bringing the DSB ends back into proximity for repair.
- Jin H. Yang
- , Hugo B. Brandão
- & Anders S. Hansen
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Article
| Open AccessHistone demethylase KDM2A is a selective vulnerability of cancers relying on alternative telomere maintenance
Alternative lengthening of telomeres (ALT) provides cancer cells a mechanism to sustain replicative immortality. Here, the authors identify KDM2A as a molecular vulnerability in ALT-dependent cancer cells and demonstrate its role in the resolution of ALT-specific telomere clusters via recruitment of SENP6.
- Fei Li
- , Yizhe Wang
- & Hongwu Zheng
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Article
| Open AccessThe RRM-mediated RNA binding activity in T. brucei RAP1 is essential for VSG monoallelic expression
Monoallelic VSG expression is essential for Trypanosoma brucei survival. Competition between TbRAP1’s RNA and dsDNA binding activities ensures that TbRAP1 sustains a high level expression of the active VSG while silencing other VSGs globally.
- Amit Kumar Gaurav
- , Marjia Afrin
- & Bibo Li
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Article
| Open AccessTelomere length associates with chronological age and mortality across racially diverse pulmonary fibrosis cohorts
The association of telomere length with age and mortality across racially diverse pulmonary fibrosis populations is unknown. Here, the authors show that leukocyte telomere length associates with chronologic age and is predictive of mortality in pulmonary fibrosis across racial groups.
- Ayodeji Adegunsoye
- , Chad A. Newton
- & Imre Noth
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| Open AccessDifferent NIPBL requirements of cohesin-STAG1 and cohesin-STAG2
NIPBL is considered the cohesin loader. Here, the authors report that a drastic reduction of NIPBL levels reduces chromatin-bound cohesin-STAG2 genome wide while cohesin-STAG1 increases and can still be found at CTCF-bound sites but cannot form loops.
- Dácil Alonso-Gil
- , Ana Cuadrado
- & Ana Losada
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Article
| Open AccessA non-genetic switch triggers alternative telomere lengthening and cellular immortalization in ATRX deficient cells
Mutations of ATRX are frequent in cancers that immortalize through the ALT (Alternative lengthening of telomeres) pathway. Here the authors show that ALT features are repressed in embryonic stem cells that lack ATRX but induced by continuous telomere instability triggered upon cell differentiation.
- Timothy K. Turkalo
- , Antonio Maffia
- & Dirk Hockemeyer
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Article
| Open AccessInterphase chromosomes of the Aedes aegypti mosquito are liquid crystalline and can sense mechanical cues
Within the nucleus, the genome of eukaryotes folds into partially organized three-dimensional structures specific to each organism. Here the authors perform physical simulations to study the genome architecture of Aedes aegypti, which reveal an ensemble of 3D chromosomal structures that are folded over and partially condensed, resembling liquid crystalline properties.
- Vinícius G. Contessoto
- , Olga Dudchenko
- & Michele Di Pierro
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| Open AccessHigh-throughput telomere length measurement at nucleotide resolution using the PacBio high fidelity sequencing platform
There exist challenges in quantifying the length of individual telomeres at single nucleotide resolution. Here the authors report a method to capture telomeres and accurately analyse their length in human cell lines and patient peripheral blood leukocyte samples using single-molecule real-time sequencing.
- Cheng-Yong Tham
- , LaiFong Poon
- & Shang Li
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Article
| Open AccessFunctional crosstalk between the cohesin loader and chromatin remodelers
Chromatin remodelers direct the cohesin loader to nucleosome depleted regions where cohesin accesses chromosomes. Muñoz et al. now show that the cohesin loader in turn is a biochemical activator of a chromatin remodeler, helping to clear nucleosomes
- Sofía Muñoz
- , Andrew Jones
- & Frank Uhlmann
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| Open AccessPolyploidy, regular patterning of genome copies, and unusual control of DNA partitioning in the Lyme disease spirochete
The bacterium Borrelia burgdorferi, which causes Lyme disease and is transmitted by ticks, has a linear chromosome and multiple plasmids. Here, Takacs et al. show that the pathogen is polyploid, the number of genome copies decreases during stationary phase, and chromosome copies are regularly spaced along the cell’s length.
- Constantin N. Takacs
- , Jenny Wachter
- & Christine Jacobs-Wagner
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Article
| Open AccessCentromere defects, chromosome instability, and cGAS-STING activation in systemic sclerosis
Fibrosis of the skin plays an important role in scleroderma. Here the authors demonstrate genetic and epigenetic abnormalities at the centromere that affect the replication of the chromosomes, resulting in activation of pathways involved in inflammation and fibrosis
- Souren Paul
- , Mark H. Kaplan
- & Rafael Contreras-Galindo
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Article
| Open AccessThe first mitotic division of human embryos is highly error prone
Human beings arise from serial mitotic divisions of a single fertilised egg. Here through live cell imaging of fertilized embryos the authors show that the first mitotic division is error prone and can contribute to preimplantation mosaicism.
- Cerys E. Currie
- , Emma Ford
- & Andrew D. McAinsh
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Article
| Open AccessFRET-FISH probes chromatin compaction at individual genomic loci in single cells
Chromatin compaction affects many nuclear processes yet compaction levels at individual genomic loci have been notoriously difficult to assess. Here, Ana Mota and co-authors from the Bienko-Crosetto Lab present FRET-FISH for probing chromatin compaction at selected loci in single cells.
- Ana Mota
- , Szymon Berezicki
- & Magda Bienko
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Article
| Open AccessPathogenic variants in SLF2 and SMC5 cause segmented chromosomes and mosaic variegated hyperploidy
The SMC5/6 complex is critical for genome stability. Here, the authors identify mutations in SLF2 and SMC5 as cause of Atelís Syndrome characterized by microcephaly, short stature, anemia, segmented chromosomes and mosaic variegated hyperploidy.
- Laura J. Grange
- , John J. Reynolds
- & Grant S. Stewart
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Article
| Open AccessSublinear scaling of the cellular proteome with ploidy
Increasing the number of chromosome sets alters the physiology of cells. Here, the authors show that although the number of chromosome sets increases, the proteome does not scale linearly with the increasing ploidy.
- G. Yahya
- , P. Menges
- & Z. Storchova
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Article
| Open AccessJoint control of meiotic crossover patterning by the synaptonemal complex and HEI10 dosage
During meiosis, the number and distribution of crossovers (COs) are tightly controlled, but the mechanistic basis of this control is unclear. Here, by combining experimental data and mathematical modeling, the study advocates a CO patterning model via coarsening through the diffusion of HEI10 along the synaptonemal complex.
- Stéphanie Durand
- , Qichao Lian
- & Raphael Mercier
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Article
| Open AccessConsequences of telomere dysfunction in fibroblasts, club and basal cells for lung fibrosis development
Telomere dysfunction induced by TRF1 depletion in fibroblasts, club and basal cells did not lead to interstitial lung fibrosis, underscoring alveolar type II cells as the relevant cell type in pulmonary fibrosis.
- Sergio Piñeiro-Hermida
- , Paula Martínez
- & Maria A. Blasco
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Article
| Open AccessXPF activates break-induced telomere synthesis
Here the authors show TERRA R-loops recruit the endonuclease XPF to telomeres, leading to DNA double-strand breaks to activate break-induced telomere synthesis at telomeres that utilize the alternative lengthening of telomeres (ALT) pathway to extend their telomeres independent of telomerase.
- Chia-Yu Guh
- , Hong-Jhih Shen
- & Hsueh-Ping Catherine Chu
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Article
| Open AccessHuman centromere repositioning activates transcription and opens chromatin fibre structure
In this study, using a human neocentromere as a model, the authors show that centromeres have a special chromatin structure. Centromere repositioning triggers transcriptional activation, epigenetic remodelling and chromatin fibre decompaction.
- Catherine Naughton
- , Covadonga Huidobro
- & Nick Gilbert
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Article
| Open AccessDAXX-ATRX regulation of p53 chromatin binding and DNA damage response
The tumor suppressor proteins DAXX and ATRX are frequently mutated in cancers with alternative lengthening of telomeres (ALT). This study shows that DAXX-ATRX regulates p53 chromatin accessibility and DNA damage response and that disruption of this pathway is critical for ALT cell survival.
- Nitish Gulve
- , Chenhe Su
- & Paul. M. Lieberman
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Article
| Open AccessHistone H3K36me2 and H3K36me3 form a chromatin platform essential for DNMT3A-dependent DNA methylation in mouse oocytes
DNMT3A is known to methylate DNA at histone H3 lysine 36 (H3K36me3)-marked transcriptionally active regions in mouse oocytes. Here the authors show that DNMT3A is also guided by H3K36me2 to methylate broad domains in genic and intergenic loci, as well as on the X chromosome. These two histone marks together comprise the minimal chromatin signature for global DNA methylation in mouse oocytes.
- Seiichi Yano
- , Takashi Ishiuchi
- & Hiroyuki Sasaki
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Article
| Open AccessThe mechanism of replication stalling and recovery within repetitive DNA
DNA replication of repetitive sequences was recreated in a test tube using purified components. DNA alone was sufficient to induce stalling. Both stalling and recovery were dictated by the capacity of DNA to fold into unusual secondary structures.
- Corella S. Casas-Delucchi
- , Manuel Daza-Martin
- & Gideon Coster
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Article
| Open AccessInterchromosomal interaction of homologous Stat92E alleles regulates transcriptional switch during stem-cell differentiation
Asymmetric inheritance of organelles, proteins and RNAs occurs during stem cell division. Here the authors show the strength of pairing of homologous Stat92E loci, a stem cell-specific gene, changes immediately after the asymmetric division due to asymmetric inheritance of new histones to one of the daughter cells and is important for turning off gene expression in this cell as it differentiates.
- Matthew Antel
- , Romir Raj
- & Mayu Inaba
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Article
| Open AccessThe megabase-scale crossover landscape is largely independent of sequence divergence
The frequency of recombination varies along chromosomes and highly correlates with sequence divergence. Here, the authors show that polymorphisms are not a major determinant of the megabase-scale recombination landscape in Arabidopsis, which is rather determined by chromatin accessibility and DNA methylation.
- Qichao Lian
- , Victor Solier
- & Raphael Mercier