Three-dimensional genome organization in epigenetic regulations: cause or consequence?

The eukaryotic genome is a complex three-dimensional entity residing in the nucleus. We present evidence that Pol III–transcribed genes such as tRNA and 5S rRNA genes can localize to centromeres and contribute to a global genome organization. Furthermore, we find that ectopic insertion of Pol III genes into a non-Pol III gene locus results in the centromeric localization of the locus. We show that the centromeric localization of Pol III genes is mediated by condensin, which interacts with the Pol III transcription machinery, and that transcription levels of the Pol III genes are negatively correlated with the centromeric localization of Pol III genes. This centromeric localization of Pol III genes initially observed in interphase becomes prominent during mitosis, when chromosomes are condensed. Remarkably, defective mitotic chromosome condensation by a condensin mutation, cut3-477, which reduces the centromeric localization of Pol III genes, is suppressed by a mutation in the sfc3 gene encoding the Pol III transcription factor TFIIIC subunit, sfc3-1. The sfc3-1 mutation promotes the centromeric localization of Pol III genes. Our study suggests there are functional links between the process of the centromeric localization of dispersed Pol III genes, their transcription, and the assembly of condensed mitotic chromosomes.

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Technologies to study spatial genome organization: beyond 3C

Briefings in Functional Genomics ◽

10.1093/bfgp/elz019 ◽

2019 ◽

Author(s):

Nadine Übelmesser ◽

Argyris Papantonis

Keyword(s):

Genome Organization ◽

Nuclear Organization ◽

Three Dimensional ◽

Nuclear Space ◽

Chromosome Conformation ◽

Novel Variants ◽

Cell Processes ◽

Systematic Biases ◽

And Function ◽

Spatial Genome Organization

Abstract The way that chromatin is organized in three-dimensional nuclear space is now acknowledged as a factor critical for the major cell processes, like transcription, replication and cell division. Researchers have been armed with new molecular and imaging technologies to study this structure-to-function link of genomes, spearheaded by the introduction of the ‘chromosome conformation capture’ technology more than a decade ago. However, this technology is not without shortcomings, and novel variants and orthogonal approaches are being developed to overcome these. As a result, the field of nuclear organization is constantly fueled by methods of increasing resolution and/or throughput that strive to eliminate systematic biases and increase precision. In this review, we attempt to highlight the most recent advances in technology that promise to provide novel insights on how chromosomes fold and function.

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Seeing Is Believing: ORCA Allows Visualization of Three-Dimensional Genome Organization at Single-Cell Resolution

Biochemistry ◽

10.1021/acs.biochem.9b00611 ◽

2019 ◽

Vol 58 (33) ◽

pp. 3477-3479 ◽

Cited By ~ 2

Author(s):

Hsiao-Lin V. Wang ◽

Victor G. Corces

Keyword(s):

Single Cell ◽

Genome Organization ◽

Three Dimensional

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3D genome organization during lymphocyte development and activation

Briefings in Functional Genomics ◽

10.1093/bfgp/elz030 ◽

2019 ◽

Vol 19 (2) ◽

pp. 71-82 ◽

Cited By ~ 1

Author(s):

Anne van Schoonhoven ◽

Danny Huylebroeck ◽

Rudi W Hendriks ◽

Ralph Stadhouders

Keyword(s):

Genome Organization ◽

Transcriptional Control ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Three Dimensional ◽

Lymphocyte Development ◽

Control Of Gene Expression ◽

3D Genome ◽

Wide Range ◽

3D Architecture

Abstract Chromosomes have a complex three-dimensional (3D) architecture comprising A/B compartments, topologically associating domains and promoter–enhancer interactions. At all these levels, the 3D genome has functional consequences for gene transcription and therefore for cellular identity. The development and activation of lymphocytes involves strict control of gene expression by transcription factors (TFs) operating in a three-dimensionally organized chromatin landscape. As lymphocytes are indispensable for tissue homeostasis and pathogen defense, and aberrant lymphocyte activity is involved in a wide range of human morbidities, acquiring an in-depth understanding of the molecular mechanisms that control lymphocyte identity is highly relevant. Here we review current knowledge of the interplay between 3D genome organization and transcriptional control during B and T lymphocyte development and antigen-dependent activation, placing special emphasis on the role of TFs.

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The three-dimensional genome organization of Drosophila melanogaster through data integration

Genome Biology ◽

10.1186/s13059-017-1264-5 ◽

2017 ◽

Vol 18 (1) ◽

Cited By ~ 38

Author(s):

Qingjiao Li ◽

Harianto Tjong ◽

Xiao Li ◽

Ke Gong ◽

Xianghong Jasmine Zhou ◽

...

Keyword(s):

Drosophila Melanogaster ◽

Data Integration ◽

Genome Organization ◽

Genome Structure ◽

Three Dimensional ◽

Structural Features ◽

Embryonic Cells ◽

Data Types ◽

Chromosome Conformation ◽

Topological Domains

Abstract Background Genome structures are dynamic and non-randomly organized in the nucleus of higher eukaryotes. To maximize the accuracy and coverage of three-dimensional genome structural models, it is important to integrate all available sources of experimental information about a genome’s organization. It remains a major challenge to integrate such data from various complementary experimental methods. Here, we present an approach for data integration to determine a population of complete three-dimensional genome structures that are statistically consistent with data from both genome-wide chromosome conformation capture (Hi-C) and lamina-DamID experiments. Results Our structures resolve the genome at the resolution of topological domains, and reproduce simultaneously both sets of experimental data. Importantly, this data deconvolution framework allows for structural heterogeneity between cells, and hence accounts for the expected plasticity of genome structures. As a case study we choose Drosophila melanogaster embryonic cells, for which both data types are available. Our three-dimensional genome structures have strong predictive power for structural features not directly visible in the initial data sets, and reproduce experimental hallmarks of the D. melanogaster genome organization from independent and our own imaging experiments. Also they reveal a number of new insights about genome organization and its functional relevance, including the preferred locations of heterochromatic satellites of different chromosomes, and observations about homologous pairing that cannot be directly observed in the original Hi-C or lamina-DamID data. Conclusions Our approach allows systematic integration of Hi-C and lamina-DamID data for complete three-dimensional genome structure calculation, while also explicitly considering genome structural variability.

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Erratum for Chowdhary et al., “Heat Shock Protein Genes Undergo Dynamic Alteration in Their Three-Dimensional Structure and Genome Organization in Response to Thermal Stress”

Molecular and Cellular Biology ◽

10.1128/mcb.00069-18 ◽

2018 ◽

Vol 38 (7) ◽

Author(s):

Surabhi Chowdhary ◽

Amoldeep S. Kainth ◽

David S. Gross

Keyword(s):

Thermal Stress ◽

Heat Shock ◽

Heat Shock Protein ◽

Genome Organization ◽

Three Dimensional ◽

Dimensional Structure ◽

Three Dimensional Structure ◽

Heat Shock Protein Genes ◽

Dynamic Alteration

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In silico prediction of high-resolution Hi-C interaction matrices

Nature Communications ◽

10.1038/s41467-019-13423-8 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 7

Author(s):

Shilu Zhang ◽

Deborah Chasman ◽

Sara Knaack ◽

Sushmita Roy

Keyword(s):

High Resolution ◽

Genome Organization ◽

Three Dimensional ◽

Predictive Performance ◽

Computational Prediction ◽

3D Genome ◽

Genome Wide ◽

Binding Factor ◽

Sequence Elements ◽

Individual Locus

AbstractThe three-dimensional (3D) organization of the genome plays an important role in gene regulation bringing distal sequence elements in 3D proximity to genes hundreds of kilobases away. Hi-C is a powerful genome-wide technique to study 3D genome organization. Owing to experimental costs, high resolution Hi-C datasets are limited to a few cell lines. Computational prediction of Hi-C counts can offer a scalable and inexpensive approach to examine 3D genome organization across multiple cellular contexts. Here we present HiC-Reg, an approach to predict contact counts from one-dimensional regulatory signals. HiC-Reg predictions identify topologically associating domains and significant interactions that are enriched for CCCTC-binding factor (CTCF) bidirectional motifs and interactions identified from complementary sources. CTCF and chromatin marks, especially repressive and elongation marks, are most important for HiC-Reg’s predictive performance. Taken together, HiC-Reg provides a powerful framework to generate high-resolution profiles of contact counts that can be used to study individual locus level interactions and higher-order organizational units of the genome.

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