Chromosome Territory Organization within the Nucleus

Cremer, Thomas; Markaki, Yolanda; Hübner, Barbara; Zunhammer, Andreas; Strickfaden, Hilmar; Beichmanis, S.; Heß, Martin; Schermelleh, Lothar; Cremer, Christoph

doi:10.1002/3527600906.mcb.200300046.pub2

Cited by 7 publications

(3 citation statements)

References 162 publications

(162 reference statements)

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“…Chromosomes are long polymers confined inside a small volume, the cell nucleus [ 42 ]. As a result, the generic characteristics of these densely packed long polymers are very different from free isolated chains and exhibit distinct universal properties [ 41 , 43 ].…”

Section: Resultsmentioning

confidence: 99%

How epigenome drives chromatin folding and dynamics, insights from efficient coarse-grained models of chromosomes

Ghosh¹,

Jost²

2018

PLoS Comput Biol

105

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The 3D organization of chromosomes is crucial for regulating gene expression and cell function. Many experimental and polymer modeling efforts are dedicated to deciphering the mechanistic principles behind chromosome folding. Chromosomes are long and densely packed—topologically constrained—polymers. The main challenges are therefore to develop adequate models and simulation methods to investigate properly the multi spatio-temporal scales of such macromolecules. Here, we proposed a generic strategy to develop efficient coarse-grained models for self-avoiding polymers on a lattice. Accounting accurately for the polymer entanglement length and the volumic density, we show that our simulation scheme not only captures the steady-state structural and dynamical properties of the system but also tracks the same dynamics at different coarse-graining. This strategy allows a strong power-law gain in numerical efficiency and offers a systematic way to define reliable coarse-grained null models for chromosomes and to go beyond the current limitations by studying long chromosomes during an extended time period with good statistics. We use our formalism to investigate in details the time evolution of the 3D organization of chromosome 3R (20 Mbp) in drosophila during one cell cycle (20 hours). We show that a combination of our coarse-graining strategy with a one-parameter block copolymer model integrating epigenomic-driven interactions quantitatively reproduce experimental data at the chromosome-scale and predict that chromatin motion is very dynamic during the cell cycle.

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Section: Resultsmentioning

confidence: 99%

How epigenome drives chromatin folding and dynamics, insights from efficient coarse-grained models of chromosomes

Ghosh¹,

Jost²

2018

PLoS Comput Biol

105

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“…The correction methods explicitly model and remove the impact of each bias source on the Hi-C data. As the first Hi-C bias reduction method, Yaffe and Tanay [73] used a non-parametric step function with 420 unknown parameters to approximate the joint effect of restriction enzyme cutting, GC content and sequence uniqueness, and went through all possible fragment pairs (in order of 10 12 ) to obtain the corrected Hi-C data. Yaffe and Tanay's method is able to effectively remove systematic biases, and significantly increase the reproducibility between biological replicates (Figure 4E).…”

Section: Bias Reductionmentioning

confidence: 99%

“…Several key insights of chromosome organizations have been obtained by FISH studies [11]. For example, although still open to debate, it is generally accepted that interphase chromosomes at low resolution level occupy distinct regions in the cell nucleus, termed as chromosome territories [12,13]. Within chromosome territories, chromosomes form highly compact, non‐random conformations to facilitate the communication between genes and their regulatory elements [14,15].…”

Section: Introductionmentioning

confidence: 99%

Understanding spatial organizations of chromosomes via statistical analysis of Hi‐C data

Deng

Qin

et al. 2013

Quant. Biol.

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Understanding how chromosomes fold provides insights into the transcription regulation, hence, the functional state of the cell. Using the next generation sequencing technology, the recently developed Hi-C approach enables a global view of spatial chromatin organization in the nucleus, which substantially expands our knowledge about genome organization and function. However, due to multiple layers of biases, noises and uncertainties buried in the protocol of Hi-C experiments, analyzing and interpreting Hi-C data poses great challenges, and requires novel statistical methods to be developed. This article provides an overview of recent Hi-C studies and their impacts on biomedical research, describes major challenges in statistical analysis of Hi-C data, and discusses some perspectives for future research.

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The potential of 3D‐FISH and super‐resolution structured illumination microscopy for studies of 3D nuclear architecture

et al. 2012

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Three-dimensional structured illumination microscopy (3D-SIM) has opened up new possibilities to study nuclear architecture at the ultrastructural level down to the ~100 nm range. We present first results and assess the potential using 3D-SIM in combination with 3D fluorescence in situ hybridization (3D-FISH) for the topographical analysis of defined nuclear targets. Our study also deals with the concern that artifacts produced by FISH may counteract the gain in resolution. We address the topography of DAPI-stained DNA in nuclei before and after 3D-FISH, nuclear pores and the lamina, chromosome territories, chromatin domains, and individual gene loci. We also look at the replication patterns of chromocenters and the topographical relationship of Xist-RNA within the inactive X-territory. These examples demonstrate that an appropriately adapted 3D-FISH/3D-SIM approach preserves key characteristics of the nuclear ultrastructure and that the gain in information obtained by 3D-SIM yields new insights into the functional nuclear organization.

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Chromosome Territory Organization within the Nucleus

Cited by 7 publications

References 162 publications

How epigenome drives chromatin folding and dynamics, insights from efficient coarse-grained models of chromosomes

How epigenome drives chromatin folding and dynamics, insights from efficient coarse-grained models of chromosomes

Understanding spatial organizations of chromosomes via statistical analysis of Hi‐C data

The potential of 3D‐FISH and super‐resolution structured illumination microscopy for studies of 3D nuclear architecture

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