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Article ; Online: Spatial co-transcriptomics reveals discrete stages of the arbuscular mycorrhizal symbiosis.

Serrano, Karen / Bezrutczyk, Margaret / Goudeau, Danielle / Dao, Thai / O'Malley, Ronan / Malmstrom, Rex R / Visel, Axel / Scheller, Henrik V / Cole, Benjamin

Nature plants

2024 Volume 10, Issue 4, Page(s) 673–688

Abstract: The symbiotic interaction of plants with arbuscular mycorrhizal (AM) fungi is ancient and widespread. Plants provide AM fungi with carbon in exchange for nutrients and water, making this interaction a prime target for crop improvement. However, plant- ... ...

Abstract	The symbiotic interaction of plants with arbuscular mycorrhizal (AM) fungi is ancient and widespread. Plants provide AM fungi with carbon in exchange for nutrients and water, making this interaction a prime target for crop improvement. However, plant-fungal interactions are restricted to a small subset of root cells, precluding the application of most conventional functional genomic techniques to study the molecular bases of these interactions. Here we used single-nucleus and spatial RNA sequencing to explore both Medicago truncatula and Rhizophagus irregularis transcriptomes in AM symbiosis at cellular and spatial resolution. Integrated, spatially registered single-cell maps revealed infected and uninfected plant root cell types. We observed that cortex cells exhibit distinct transcriptome profiles during different stages of colonization by AM fungi, indicating dynamic interplay between both organisms during establishment of the cellular interface enabling successful symbiosis. Our study provides insight into a symbiotic relationship of major agricultural and environmental importance and demonstrates a paradigm combining single-cell and spatial transcriptomics for the analysis of complex organismal interactions.
Language	English
Publishing date	2024-04-08
Publishing country	England
Document type	Journal Article
ISSN	2055-0278
ISSN (online)	2055-0278
DOI	10.1038/s41477-024-01666-3
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Power in isolation: insights from single cells.

Cole, Benjamin J / Basso, Jonelle T R / Visel, Axel

Nature reviews. Microbiology

2020 Volume 18, Issue 7, Page(s) 364

MeSH term(s)	Bacteria/genetics ; Bacteria/metabolism ; DNA Transposable Elements/genetics ; Flow Cytometry/methods ; Genome, Bacterial/genetics ; RNA-Seq/methods ; Single-Cell Analysis/methods ; Transcriptome/genetics
Chemical Substances	DNA Transposable Elements
Language	English
Publishing date	2020-05-06
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2139054-X
ISSN	1740-1534 ; 1740-1526
ISSN (online)	1740-1534
ISSN	1740-1526
DOI	10.1038/s41579-020-0381-4
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Zs.A 5865: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 74: Show issues

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Article ; Online: Perfect and imperfect views of ultraconserved sequences.

Snetkova, Valentina / Pennacchio, Len A / Visel, Axel / Dickel, Diane E

Nature reviews. Genetics

2021 Volume 23, Issue 3, Page(s) 182–194

Abstract: Across the human genome, there are nearly 500 'ultraconserved' elements: regions of at least 200 contiguous nucleotides that are perfectly conserved in both the mouse and rat genomes. Remarkably, the majority of these sequences are non-coding, and many ... ...

Abstract	Across the human genome, there are nearly 500 'ultraconserved' elements: regions of at least 200 contiguous nucleotides that are perfectly conserved in both the mouse and rat genomes. Remarkably, the majority of these sequences are non-coding, and many can function as enhancers that activate tissue-specific gene expression during embryonic development. From their first description more than 15 years ago, their extreme conservation has both fascinated and perplexed researchers in genomics and evolutionary biology. The intrigue around ultraconserved elements only grew with the observation that they are dispensable for viability. Here, we review recent progress towards understanding the general importance and the specific functions of ultraconserved sequences in mammalian development and human disease and discuss possible explanations for their extreme conservation.
MeSH term(s)	Animals ; Conserved Sequence/physiology ; Embryonic Development/genetics ; Enhancer Elements, Genetic ; Female ; Genome/genetics ; Genomics/methods ; Genomics/trends ; History, 21st Century ; Humans ; Mammals/genetics ; Mice ; Pregnancy ; Rats
Language	English
Publishing date	2021-11-11
Publishing country	England
Document type	Historical Article ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	2035157-4
ISSN	1471-0064 ; 1471-0056
ISSN (online)	1471-0064
ISSN	1471-0056
DOI	10.1038/s41576-021-00424-x
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Zs.A 5474: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 40: Show issues

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Article ; Online: Identification of conserved skeletal enhancers associated with craniosynostosis risk genes.

He 何璇, Xuan Anita / Berenson, Anna / Bernard, Michelle / Weber, Chris / Cook, Laura / Visel, Axel / Fuxman Bass, Juan I / Fisher, Shannon

Human molecular genetics

2023

Abstract: Craniosynostosis, defined by premature fusion of one or multiple cranial sutures, is a common congenital defect affecting more than 1/2000 infants and results in restricted brain expansion. Single gene mutations account for 15-20% of cases, largely as ... ...

Abstract	Craniosynostosis, defined by premature fusion of one or multiple cranial sutures, is a common congenital defect affecting more than 1/2000 infants and results in restricted brain expansion. Single gene mutations account for 15-20% of cases, largely as part of a syndrome, but the majority are nonsyndromic with complex underlying genetics. We hypothesized that the two noncoding genomic regions identified by a GWAS for craniosynostosis contain distal regulatory elements for the risk genes BMPER and BMP2. To identify such regulatory elements, we surveyed conserved noncoding sequences from both risk loci for enhancer activity in transgenic Danio rerio. We identified enhancers from both regions that direct expression to skeletal tissues, consistent with the endogenous expression of bmper and bmp2. For each locus, we also found a skeletal enhancer that also contains a sequence variant associated with craniosynostosis risk. We examined the activity of each enhancer during craniofacial development and found that the BMPER-associated enhancer is active in the restricted region of cartilage closely associated with frontal bone initiation. The same enhancer is active in mouse skeletal tissues, demonstrating evolutionarily conserved activity. Using enhanced yeast one-hybrid assays, we identified transcription factors that bind each enhancer and observed differential binding between alleles, implicating multiple signaling pathways. Our findings help unveil the genetic mechanism of the two craniosynostosis risk loci. More broadly, our combined in vivo approach is applicable to many complex genetic diseases to build a link between association studies and specific genetic mechanisms.
Language	English
Publishing date	2023-10-26
Publishing country	England
Document type	Journal Article
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/ddad182
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Zs.A 3469: Show issues

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Article ; Online: Increased enhancer-promoter interactions during developmental enhancer activation in mammals.

Chen, Zhuoxin / Snetkova, Valentina / Bower, Grace / Jacinto, Sandra / Clock, Benjamin / Dizehchi, Atrin / Barozzi, Iros / Mannion, Brandon J / Alcaina-Caro, Ana / Lopez-Rios, Javier / Dickel, Diane E / Visel, Axel / Pennacchio, Len A / Kvon, Evgeny Z

Nature genetics

2024 Volume 56, Issue 4, Page(s) 675–685

Abstract: Remote enhancers are thought to interact with their target promoters via physical proximity, yet the importance of this proximity for enhancer function remains unclear. Here we investigate the three-dimensional (3D) conformation of enhancers during ... ...

Abstract	Remote enhancers are thought to interact with their target promoters via physical proximity, yet the importance of this proximity for enhancer function remains unclear. Here we investigate the three-dimensional (3D) conformation of enhancers during mammalian development by generating high-resolution tissue-resolved contact maps for nearly a thousand enhancers with characterized in vivo activities in ten murine embryonic tissues. Sixty-one percent of developmental enhancers bypass their neighboring genes, which are often marked by promoter CpG methylation. The majority of enhancers display tissue-specific 3D conformations, and both enhancer-promoter and enhancer-enhancer interactions are moderately but consistently increased upon enhancer activation in vivo. Less than 14% of enhancer-promoter interactions form stably across tissues; however, these invariant interactions form in the absence of the enhancer and are likely mediated by adjacent CTCF binding. Our results highlight the general importance of enhancer-promoter physical proximity for developmental gene activation in mammals.
MeSH term(s)	Animals ; Mice ; Enhancer Elements, Genetic/genetics ; Promoter Regions, Genetic/genetics ; Transcriptional Activation/genetics ; Mammals/genetics ; Chromatin/genetics
Chemical Substances	Chromatin
Language	English
Publishing date	2024-03-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/s41588-024-01681-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 3613: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 46: Show issues

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Article ; Online: Induction of kidney-related gene programs through co-option of SALL1 in mole ovotestes.

Schindler, Magdalena / Osterwalder, Marco / Harabula, Izabela / Wittler, Lars / Tzika, Athanasia C / Dechmann, Dina K N / Vingron, Martin / Visel, Axel / Haas, Stefan A / Real, Francisca M

Development (Cambridge, England)

2023 Volume 150, Issue 17

Abstract: Changes in gene expression represent an important source of phenotypic innovation. Yet how such changes emerge and impact the evolution of traits remains elusive. Here, we explore the molecular mechanisms associated with the development of masculinizing ... ...

Abstract	Changes in gene expression represent an important source of phenotypic innovation. Yet how such changes emerge and impact the evolution of traits remains elusive. Here, we explore the molecular mechanisms associated with the development of masculinizing ovotestes in female moles. By performing integrative analyses of epigenetic and transcriptional data in mole and mouse, we identified the co-option of SALL1 expression in mole ovotestes formation. Chromosome conformation capture analyses highlight a striking conservation of the 3D organization at the SALL1 locus, but an evolutionary divergence of enhancer activity. Interspecies reporter assays support the capability of mole-specific enhancers to activate transcription in urogenital tissues. Through overexpression experiments in transgenic mice, we further demonstrate the capability of SALL1 to induce kidney-related gene programs, which are a signature of mole ovotestes. Our results highlight the co-option of gene expression, through changes in enhancer activity, as a plausible mechanism for the evolution of traits.
MeSH term(s)	Animals ; Female ; Mice ; Kidney/metabolism ; Mice, Transgenic ; Moles/genetics
Language	English
Publishing date	2023-09-01
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	90607-4
ISSN	1477-9129 ; 0950-1991
ISSN (online)	1477-9129
ISSN	0950-1991
DOI	10.1242/dev.201562
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Ub I Zs.183: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 91: Show issues

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Article ; Online: Identification of ancestral gnathostome Gli3 enhancers with activity in mammals.

Ali, Shahid / Abrar, Muhammad / Hussain, Irfan / Batool, Fatima / Raza, Rabail Zehra / Khatoon, Hizran / Zoia, Matteo / Visel, Axel / Shubin, Neil H / Osterwalder, Marco / Abbasi, Amir Ali

Development, growth & differentiation

2023 Volume 66, Issue 1, Page(s) 75–88

Abstract: Abnormal expression of the transcriptional regulator and hedgehog (Hh) signaling pathway effector Gli3 is known to trigger congenital disease, most frequently affecting the central nervous system (CNS) and the limbs. Accurate delineation of the genomic ... ...

Abstract	Abnormal expression of the transcriptional regulator and hedgehog (Hh) signaling pathway effector Gli3 is known to trigger congenital disease, most frequently affecting the central nervous system (CNS) and the limbs. Accurate delineation of the genomic cis-regulatory landscape controlling Gli3 transcription during embryonic development is critical for the interpretation of noncoding variants associated with congenital defects. Here, we employed a comparative genomic analysis on fish species with a slow rate of molecular evolution to identify seven previously unknown conserved noncoding elements (CNEs) in Gli3 intronic intervals (CNE15-21). Transgenic assays in zebrafish revealed that most of these elements drive activities in Gli3 expressing tissues, predominantly the fins, CNS, and the heart. Intersection of these CNEs with human disease associated SNPs identified CNE15 as a putative mammalian craniofacial enhancer, with conserved activity in vertebrates and potentially affected by mutation associated with human craniofacial morphology. Finally, comparative functional dissection of an appendage-specific CNE conserved in slowly evolving fish (elephant shark), but not in teleost (CNE14/hs1586) indicates co-option of limb specificity from other tissues prior to the divergence of amniotes and lobe-finned fish. These results uncover a novel subset of intronic Gli3 enhancers that arose in the common ancestor of gnathostomes and whose sequence components were likely gradually modified in other species during the process of evolutionary diversification.
MeSH term(s)	Animals ; Humans ; Zebrafish/genetics ; Zebrafish/metabolism ; Enhancer Elements, Genetic/genetics ; Hedgehog Proteins/genetics ; Hedgehog Proteins/metabolism ; Animals, Genetically Modified ; Mammals ; Evolution, Molecular ; Conserved Sequence/genetics
Chemical Substances	Hedgehog Proteins
Language	English
Publishing date	2023-12-20
Publishing country	Japan
Document type	Journal Article
ZDB-ID	280433-5
ISSN	1440-169X ; 0012-1592
ISSN (online)	1440-169X
ISSN	0012-1592
DOI	10.1111/dgd.12901
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 194: Show issues

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Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

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Book ; Online ; Thesis: Genomische Untersuchungen zur Cortexentwicklung der Maus

Visel, Axel

2004

Abstract: Adenylate cyclases, cerebral cortex, in situ- ... ...

Author's details	von Axel Visel
Abstract	Adenylate cyclases, cerebral cortex, in situ-hybridization
Language	German
Size	Online-Ressource (116 p. = 9106 Kb)
Edition	[Elektronische Ressource]
Publisher	Universitätsbibliothek u. Technische Informationsbibliothek
Publishing place	Hannover
Document type	Book ; Online ; Thesis
Thesis / German Habilitation thesis	Univ., Diss.--Hannover, 2004
Database	Former special subject collection: coastal and deep sea fishing

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Book ; Online ; Thesis: Genomische Untersuchungen zur Cortexentwicklung der Maus

Visel, Axel

2004

Abstract: Adenylate cyclases, cerebral cortex, in situ- ... ...

Author's details	von Axel Visel
Abstract	Adenylate cyclases, cerebral cortex, in situ-hybridization
Language	German
Size	Online-Ressource (116 p. = 9106 Kb)
Edition	[Elektronische Ressource]
Publisher	Universitätsbibliothek u. Technische Informationsbibliothek
Publishing place	Hannover
Document type	Book ; Online ; Thesis
Thesis / German Habilitation thesis	Univ., Diss.--Hannover, 2004
Database	Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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Article: Stable enhancers are active in development, and fragile enhancers are associated with evolutionary adaptation

Li, Shan / Kvon, Evgeny Z / Visel, Axel / Pennacchio, Len A / Ovcharenko, Ivan

Genome biology. 2019 Dec., v. 20, no. 1

2019

Abstract: BACKGROUND: Despite continual progress in the identification and characterization of trait- and disease-associated variants that disrupt transcription factor (TF)-DNA binding, little is known about the distribution of TF binding deactivating mutations ( ... ...

Abstract	BACKGROUND: Despite continual progress in the identification and characterization of trait- and disease-associated variants that disrupt transcription factor (TF)-DNA binding, little is known about the distribution of TF binding deactivating mutations (deMs) in enhancer sequences. Here, we focus on elucidating the mechanism underlying the different densities of deMs in human enhancers. RESULTS: We identify two classes of enhancers based on the density of nucleotides prone to deMs. Firstly, fragile enhancers with abundant deM nucleotides are associated with the immune system and regular cellular maintenance. Secondly, stable enhancers with only a few deM nucleotides are associated with the development and regulation of TFs and are evolutionarily conserved. These two classes of enhancers feature different regulatory programs: the binding sites of pioneer TFs of FOX family are specifically enriched in stable enhancers, while tissue-specific TFs are enriched in fragile enhancers. Moreover, stable enhancers are more tolerant of deMs due to their dominant employment of homotypic TF binding site (TFBS) clusters, as opposed to the larger-extent usage of heterotypic TFBS clusters in fragile enhancers. Notably, the sequence environment and chromatin context of the cognate motif, other than the motif itself, contribute more to the susceptibility to deMs of TF binding. CONCLUSIONS: This dichotomy of enhancer activity is conserved across different tissues, has a specific footprint in epigenetic profiles, and argues for a bimodal evolution of gene regulatory programs in vertebrates. Specifically encoded stable enhancers are evolutionarily conserved and associated with development, while differently encoded fragile enhancers are associated with the adaptation of species.
Keywords	binding sites ; chromatin ; enhancer elements ; epigenetics ; evolutionary adaptation ; genes ; humans ; immune system ; mutation ; nucleotides ; tissues ; transcription factors
Language	English
Dates of publication	2019-12
Size	p. 140.
Publishing place	BioMed Central
Document type	Article
ZDB-ID	2040529-7
ISSN	1474-760X ; 1465-6906
ISSN (online)	1474-760X
ISSN	1465-6906
DOI	10.1186/s13059-019-1750-z
Database	NAL-Catalogue (AGRICOLA)

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