Mapping the 3D genome: Aiming for consilience

Dekker, Job

doi:10.1038/nrm.2016.151

Cited by 55 publications

(58 citation statements)

References 4 publications

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“…This likely reflects the fact that total Hi-C read number is normalized between samples (so increased inter-TAD signal must be compensated by decreased signal elsewhere) while FISH distances are less resolutive but absolute – a limitation in comparing Hi-C and FISH (Dekker, 2016; Fudenberg and Imakaev, 2016; Giorgetti and Heard, 2016). …”

Section: Resultsmentioning

confidence: 99%

Targeted Degradation of CTCF Decouples Local Insulation of Chromosome Domains from Genomic Compartmentalization

Nora

Goloborodko

Valton

et al. 2017

Cell

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1,467

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1,735

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Summary The molecular mechanisms underlying folding of mammalian chromosomes remain poorly understood. The transcription factor CTCF is a candidate regulator of chromosomal structure. Using the auxin-inducible degron system in mouse embryonic stem cells, we show that CTCF is absolutely and dose-dependently required for looping between CTCF target sites and insulation of topologically associating domains (TADs). Restoring CTCF reinstates proper architecture on altered chromosomes, indicating a powerful instructive function for CTCF in chromatin folding. CTCF remains essential for TAD organization in non-dividing cells. Surprisingly, active and inactive genome compartments remain properly segregated upon CTCF depletion, revealing that compartmentalization of mammalian chromosomes emerges independently of proper insulation of TADs. Further, our data support that CTCF mediates transcriptional insulator function through enhancer-blocking but not as a direct barrier to heterochromatin spreading. Beyond defining the functions of CTCF in chromosome folding these results provide new fundamental insights into the rules governing mammalian genome organization.

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Section: Resultsmentioning

confidence: 99%

Targeted Degradation of CTCF Decouples Local Insulation of Chromosome Domains from Genomic Compartmentalization

Nora

Goloborodko

Valton

et al. 2017

Cell

Self Cite

1,467

179

1,735

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“…Because SPRITE does not rely on proximity ligation, which requires two DNA sites to be close enough to form a ligation junction (Dekker, 2016; Giorgetti and Heard, 2016), we reasoned that SPRITE might identify additional interactions that occur at further nuclear distances than those identified by Hi-C (Figure 3A). Indeed, we noticed that the number of pairwise contacts observed between two genomic regions as a function of their linear genomic distance (“distance decay”) occurs at different rates when comparing the Hi-C and SPRITE data (Figure S3A).…”

Section: Resultsmentioning

confidence: 99%

“…Specifically, microscopy measures the 3D spatial distances between DNA sites within single cells, whereas proximity-ligation measures the frequency with which two DNA sites are close enough in the nucleus to directly ligate (Dekker, 2016). This difference is particularly significant when considering DNA regions that organize around nuclear bodies, which can range in size from 0.5-2μm (Pederson, 2011), and therefore may be too far apart to directly ligate.…”

Section: Introductionmentioning

confidence: 99%

Higher-Order Inter-chromosomal Hubs Shape 3D Genome Organization in the Nucleus

Quinodoz

Ollikainen

Tabak

et al. 2018

Cell

728

814

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Eukaryotic genomes are packaged into a 3-dimensional structure in the nucleus. Current methods for studying genome-wide structure are based on proximity ligation. However, this approach can fail to detect known structures, such as interactions with nuclear bodies, because these DNA regions can be too far apart to directly ligate. Accordingly, our overall understanding of genome organization remains incomplete. Here, we develop split-pool recognition of interactions by tag extension (SPRITE), a method that enables genome-wide detection of higher-order interactions within the nucleus. Using SPRITE, we recapitulate known structures identified by proximity ligation and identify additional interactions occurring across larger distances, including two hubs of inter-chromosomal interactions that are arranged around the nucleolus and nuclear speckles. We show that a substantial fraction of the genome exhibits preferential organization relative to these nuclear bodies. Our results generate a global model whereby nuclear bodies act as inter-chromosomal hubs that shape the overall packaging of DNA in the nucleus.

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“…Alternatively, C-technologies in combination with high-throughput sequencing can provide a genome-wide view of chromatin organization from populations of cells but might overlook cell-to-cell variations. The imaging-based technologies and C-technologies therefore provide complementary views of 3D genome organization, despite some discrepancies at specific regions (Dekker 2016, Williamson et al 2014). …”

Section: Tools To Explore 3d Genome Organizationmentioning

confidence: 99%

The Three-Dimensional Organization of Mammalian Genomes

Ren

2017

Annu. Rev. Cell Dev. Biol.

331

284

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Animal development depends on not only the linear genome sequence that embeds millions of cis-regulatory elements, but also the three-dimensional (3D) chromatin architecture that orchestrates the interplay between cis-regulatory elements and their target genes. Compared to our knowledge of the cis-regulatory sequences, the understanding of the 3D genome organization in human and other eukaryotes is still limited. Recent advances in technologies to map the 3D genome architecture have greatly accelerated the pace of discovery. Here, we review emerging concepts of chromatin organization in mammalian cells, discuss the dynamics of chromatin conformation during development, and highlight important roles for chromatin organization in cancer and other human diseases.

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Mapping the 3D genome: Aiming for consilience

Cited by 55 publications

References 4 publications

Targeted Degradation of CTCF Decouples Local Insulation of Chromosome Domains from Genomic Compartmentalization

Targeted Degradation of CTCF Decouples Local Insulation of Chromosome Domains from Genomic Compartmentalization

Higher-Order Inter-chromosomal Hubs Shape 3D Genome Organization in the Nucleus

The Three-Dimensional Organization of Mammalian Genomes

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