High-resolution TADs reveal DNA sequences underlying genome organization in flies

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

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Mechanisms of Interplay between Transcription Factors and the 3D Genome

Molecular Cell, Journal Year: 2019, Volume and Issue: 76(2), P. 306 - 319

Published: Sept. 11, 2019

Language: Английский

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Coaching from the sidelines: the nuclear periphery in genome regulation

Nature Reviews Genetics, Journal Year: 2018, Volume and Issue: 20(1), P. 39 - 50

Published: Oct. 24, 2018

Language: Английский

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Nuclear transport proteins: structure, function, and disease relevance

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Nov. 10, 2023

Abstract Proper subcellular localization is crucial for the functioning of biomacromolecules, including proteins and RNAs. Nuclear transport a fundamental cellular process that regulates many macromolecules within nuclear or cytoplasmic compartments. In humans, approximately 60 are involved in transport, nucleoporins form membrane-embedded pore complexes, karyopherins cargoes through these Ran system ensure directed rapid transport. Many play additional essential roles mitosis, biomolecular condensation, gene transcription. Dysregulation linked to major human diseases such as cancer, neurodegenerative diseases, viral infections. Selinexor (KPT-330), an inhibitor targeting export factor XPO1 (also known CRM1), was approved 2019 treat two types blood cancers, dozens clinical trials ongoing. This review summarizes three decades research data this field but focuses on structure function individual from recent studies, providing cutting-edge holistic view role health disease. In-depth knowledge rapidly evolving has potential bring new insights into biology, pathogenic mechanisms, therapeutic approaches.

Language: Английский

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Core Components of the Nuclear Pore Bind Distinct States of Chromatin and Contribute to Polycomb Repression

Molecular Cell, Journal Year: 2019, Volume and Issue: 77(1), P. 67 - 81.e7

Published: Nov. 26, 2019

Language: Английский

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WNT signaling and AHCTF1 promote oncogenic MYC expression through super-enhancer-mediated gene gating

Nature Genetics, Journal Year: 2019, Volume and Issue: 51(12), P. 1723 - 1731

Published: Nov. 29, 2019

Language: Английский

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One Ring to Rule them All? Structural and Functional Diversity in the Nuclear Pore Complex

Trends in Biochemical Sciences, Journal Year: 2021, Volume and Issue: 46(7), P. 595 - 607

Published: Feb. 7, 2021

Language: Английский

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Nucleoporin Seh1 Interacts with Olig2/Brd7 to Promote Oligodendrocyte Differentiation and Myelination

Neuron, Journal Year: 2019, Volume and Issue: 102(3), P. 587 - 601.e7

Published: March 12, 2019

Language: Английский

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Nucleoporin 153 links nuclear pore complex to chromatin architecture by mediating CTCF and cohesin binding

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: May 25, 2020

Abstract Nucleoporin proteins (Nups) have been proposed to mediate spatial and temporal chromatin organization during gene regulation. Nevertheless, the molecular mechanisms in mammalian cells are not well understood. Here, we report that 153 (NUP153) interacts with architectural proteins, CTCF cohesin, mediates their binding across cis -regulatory elements TAD boundaries mouse embryonic stem (ES) cells. NUP153 depletion results altered cohesin differential expression — specifically at bivalent developmental genes. To investigate mechanism, utilize epidermal growth factor (EGF)-inducible immediate early genes (IEGs). We find controls POL II pausing basal state. Furthermore, efficient IEG transcription relies on NUP153. propose links nuclear pore complex (NPC) architecture allowing poised respond rapidly cues be properly modulated.

Language: Английский

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The dynamic three-dimensional organization of the diploid yeast genome

eLife, Journal Year: 2017, Volume and Issue: 6

Published: May 24, 2017

The budding yeast Saccharomyces cerevisiae is a long-standing model for the three-dimensional organization of eukaryotic genomes. However, even in this well-studied model, it unclear how homolog pairing diploids or environmental conditions influence overall genome organization. Here, we performed high-throughput chromosome conformation capture on diverged hybrid to obtain first global view diploid yeasts. After controlling Rabl-like orientation using polymer observe significant proximity that increases saturated culture conditions. Surprisingly, localized increase homologous interactions between HAS1-TDA1 alleles specifically under galactose induction and growth. This accompanied by relocalization nuclear periphery requires Nup2, suggesting role pore complexes. Together, these results reveal has dynamic complex 3D

Language: Английский

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