Polyploidy, the Nucleotype, and Novelty: The Impact of Genome Doubling on the Biology of the Cell DOI Open Access
Jeff J. Doyle, Jeremy E. Coate

International Journal of Plant Sciences, Journal Year: 2018, Volume and Issue: 180(1), P. 1 - 52

Published: Dec. 6, 2018

Polyploidy is a key mechanism of genome evolution and speciation, particularly in plants. Many aspects polyploidy have been elucidated with the tools that become available during molecular genetics genomics revolution. Nevertheless, significant questions remain about how doubling per se, absence hybridization, capable generating evolutionary novelty. This true at cellular level, where since discovery it has assumed increased cell size plays role physiological developmental changes associated doubling, usually through changing surface-to-volume ratio. Cell size, nuclear volume, cycle duration hypothesized to be among suite "nucleotypic" characters, defined as phenotypic traits influenced by bulk DNA amount, irrespective genic content. We update this old but still relevant concept, focusing on what current knowledge from biology can elucidate quantitative differences between diploids isogenic autopolyploids could lead differences. Much remains learned before causality correlation distinguished complex network interactions cytoplasm, nucleus other organelles, cycle, metabolism, intra- intercellular transport. It clear many effects are likely type specific conditioned different genomic architectures species which occurs. The rapidly developing ability study processes such transcription movement molecules single cells will enable experiments addressing fundamental potentially nucleotypic these interact genotypes produce

Language: Английский

Multiscale 3D Genome Rewiring during Mouse Neural Development DOI Creative Commons
Boyan Bonev, Netta Mendelson Cohen, Quentin Szabo

et al.

Cell, Journal Year: 2017, Volume and Issue: 171(3), P. 557 - 572.e24

Published: Oct. 1, 2017

Chromosome conformation capture technologies have revealed important insights into genome folding. Yet, how spatial architecture is related to gene expression and cell fate remains unclear. We comprehensively mapped 3D chromatin organization during mouse neural differentiation in vitro vivo, generating the highest-resolution Hi-C maps available date. found that transcription correlated with insulation long-range interactions, but dCas9-mediated activation insufficient for creating TAD boundaries de novo. Additionally, we discovered contacts between bodies of exon-rich, active genes all types. During differentiation, TADs become less pronounced while inactive interact more strongly. An extensive Polycomb network stem cells disrupted, dynamic interactions factors appear vivo. Finally, type-specific enhancer-promoter are established concomitant expression. This work shows multiple influence dynamics development.

Language: Английский

Citations

1237
Epigenetic plasticity and the hallmarks of cancer DOI Open Access
William Flavahan, Elizabeth Gaskell, B Bernstein

et al.

Science, Journal Year: 2017, Volume and Issue: 357(6348)

Published: July 20, 2017

Cancer epigenetics in the driver's seat Recent cancer genome projects unexpectedly highlighted role of epigenetic alterations development. About half human cancers were found to harbor mutations chromatin proteins. In a Review, Flavahan et al. propose that and aberrations have potential confer on cells full range oncogenic properties represented classic “hallmarks” depiction cancer. They suggest genetic, environmental, metabolic factors can make aberrantly permissive or restrictive. Permissive creates state “epigenetic plasticity,” which activate oncogene expression cell fate changes drive Science , this issue p. eaal2380

Language: Английский

Citations

1156
Two independent modes of chromatin organization revealed by cohesin removal DOI
Wibke Schwarzer, Nezar Abdennur, Anton Goloborodko

et al.

Nature, Journal Year: 2017, Volume and Issue: 551(7678), P. 51 - 56

Published: Sept. 27, 2017

Language: Английский

Citations

1132
GeneHancer: genome-wide integration of enhancers and target genes in GeneCards DOI Creative Commons
Simon Fishilevich, Ron Nudel, Noa Rappaport

et al.

Database, Journal Year: 2017, Volume and Issue: 2017

Published: Jan. 1, 2017

A major challenge in understanding gene regulation is the unequivocal identification of enhancer elements and uncovering their connections to genes. We present GeneHancer, a novel database human enhancers inferred target genes, framework GeneCards. First, we integrated total 434 000 reported from four different genome-wide databases: Encyclopedia DNA Elements (ENCODE), Ensembl regulatory build, functional annotation mammalian genome (FANTOM) project VISTA Enhancer Browser. Employing an integration algorithm that aims remove redundancy, GeneHancer portrays 285 candidate (covering 12.4% genome), 94 which are derived more than one source, each assigned annotation-derived confidence score. subsequently links using: tissue co-expression correlation between genes RNAs, as well enhancer-targeted transcription factor genes; expression quantitative trait loci for variants within enhancers; capture Hi-C, promoter-specific conformation assay. The individual scores based on these methods, along with gene–enhancer genomic distances, form basis GeneHancer's combinatorial likelihood-based enhancer–gene pairing. Finally, define 'elite' relations reflecting both high-likelihood definition strong association. predictions fully widely used GeneCards Suite, whereby annotations displayed every relevant GeneCard. This assists mapping non-coding enhancers, via linked forms variant–phenotype interpretation whole-genome sequences health disease. Database URL:http://www.genecards.org/

Language: Английский

Citations

1113
A Compendium of Chromatin Contact Maps Reveals Spatially Active Regions in the Human Genome DOI Creative Commons
Anthony D. Schmitt, Ming Hu, Inkyung Jung

et al.

Cell Reports, Journal Year: 2016, Volume and Issue: 17(8), P. 2042 - 2059

Published: Nov. 1, 2016

Language: Английский

Citations

850
Quantitative Proteomics of the Cancer Cell Line Encyclopedia DOI Creative Commons
David P. Nusinow,

John Szpyt,

Mahmoud Ghandi

et al.

Cell, Journal Year: 2020, Volume and Issue: 180(2), P. 387 - 402.e16

Published: Jan. 1, 2020

Language: Английский

Citations

826
High-resolution TADs reveal DNA sequences underlying genome organization in flies DOI Creative Commons
Fidel Ramírez, Vivek Bhardwaj, Laura Arrigoni

et al.

Nature Communications, Journal Year: 2018, Volume and Issue: 9(1)

Published: Jan. 9, 2018

Despite an abundance of new studies about topologically associating domains (TADs), the role genetic information in TAD formation is still not fully understood. Here we use our software, HiCExplorer (hicexplorer.readthedocs.io) to annotate >2800 high-resolution (570 bp) boundaries Drosophila melanogaster. We identify eight DNA motifs enriched at boundaries, including a motif bound by M1BP protein, and two boundary motifs. In contrast mammals, CTCF only on small fraction flanking inactive chromatin while most active contain or Beaf-32 proteins. demonstrate that can be accurately predicted using sequences open sites. propose sequence guides genome architecture allocation proteins genome. Finally, present interactive online database access explore spatial organization fly, mouse human genomes, available http://chorogenome.ie-freiburg.mpg.de .

Language: Английский

Citations

813
Structural variation in the 3D genome DOI
Malte Spielmann, Darío G. Lupiáñez, Stefan Mundlos

et al.

Nature Reviews Genetics, Journal Year: 2018, Volume and Issue: 19(7), P. 453 - 467

Published: April 24, 2018

Language: Английский

Citations

633
Eukaryotic core promoters and the functional basis of transcription initiation DOI
Vanja Haberle, Alexander Stark

Nature Reviews Molecular Cell Biology, Journal Year: 2018, Volume and Issue: 19(10), P. 621 - 637

Published: June 26, 2018

Language: Английский

Citations

633
Developmental enhancers and chromosome topology DOI Open Access
Eileen E. M. Furlong, Michael Levine

Science, Journal Year: 2018, Volume and Issue: 361(6409), P. 1341 - 1345

Published: Sept. 28, 2018

Developmental enhancers mediate on/off patterns of gene expression in specific cell types at particular stages during metazoan embryogenesis. They typically integrate multiple signals and regulatory determinants to achieve precise spatiotemporal expression. Such can map quite far—one megabase or more—from the genes they regulate. How remote relay information their target promoters is one central mysteries genome organization function. A variety contrasting mechanisms have been proposed over years, including enhancer tracking, linking, looping, mobilization transcription factories. We argue that extreme versions these cannot account for transcriptional dynamics precision seen living cells, tissues, embryos. describe emerging evidence dynamic three-dimensional hubs combine different elements classical models.

Language: Английский

Citations

587