Repeat elements organise 3D genome structure and mediate transcription in the filamentous fungus Epichloë festucae

AbstractStructural features of genomes, including the three-dimensional arrangement of DNA in the nucleus, are increasingly seen as key contributors to the regulation of gene expression. However, studies on how genome structure and nuclear organization influence transcription have so far been limited to a handful of model species. This narrow focus limits our ability to draw general conclusions about the ways in which three-dimensional structures are encoded, and to integrate information from three-dimensional data to address a broader gamut of biological questions. Here, we generate a complete and gapless genome sequence for the filamentous fungus,Epichloë festucae. Coupling it with RNAseq and HiC data, we investigate how the structure of the genome contributes to the suite of transcriptional changes that anEpichloëspecies needs to maintain symbiotic relationships with its grass host. Our results reveal a unique “patchwork” genome, in which repeat-rich blocks of DNA with discrete boundaries are interspersed by gene-rich sequences. In contrast to other species, the three-dimensional structure of the genome is anchored by these repeat blocks, which act to isolate transcription in neighbouring gene-rich regions. Genes that are differentially expressed in planta are enriched near the boundaries of these repeat-rich blocks, suggesting that their three-dimensional orientation partly encodes and regulates the symbiotic relationship formed by this organism.

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Modification of Nuclear Compartments and the 3D Genome in the Course of a Viral Infection

Acta Naturae ◽

10.32607/actanaturae.11041 ◽

2020 ◽

Vol 12 (4) ◽

pp. 34-46

Author(s):

S. V. Razin ◽

A. A. Gavrilov ◽

O. V. Iarovaia

Keyword(s):

Viral Infection ◽

Cell Nucleus ◽

Genome Structure ◽

Antiviral Defense ◽

3D Genome ◽

Nuclear Compartments ◽

Defense Systems ◽

3D Genome Structure ◽

Cellular Genome

The review addresses the question of how the structural and functional compartmentalization of the cell nucleus and the 3D organization of the cellular genome are modified during the infection of cells with various viruses. Particular attention is paid to the role of the introduced changes in the implementation of the viral strategy to evade the antiviral defense systems and provide conditions for viral replication. The discussion focuses on viruses replicating in the cell nucleus. Cytoplasmic viruses are mentioned in cases when a significant reorganization of the nuclear compartments or the 3D genome structure occurs during an infection with these viruses.

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Exploring the Effects of Genetic Variation on Gene Regulation in Cancer in the Context of 3D Genome Structure

10.21203/rs.3.rs-496328/v1 ◽

2021 ◽

Author(s):

Noha Osman ◽

Abd-El-Monsif Shawky ◽

Michal Brylinski

Keyword(s):

High Risk ◽

Genetic Variants ◽

Large Scale ◽

Target Genes ◽

Genome Structure ◽

Regulatory Elements ◽

3D Genome ◽

Risk Snps ◽

Prostate Cancers ◽

3D Genome Structure

Abstract Background: Numerous genome-wide association studies (GWAS) conducted to date revealed genetic variants associated with various diseases, including breast and prostate cancers. Despite the availability of these large-scale data, relatively few variants have been functionally characterized, mainly because the majority of single-nucleotide polymorphisms (SNPs) map to the non-coding regions of the human genome. The functional characterization of these non-coding variants and the identification of their target genes remain challenging.Results: In this communication, we explore the potential functional mechanisms of non-coding SNPs by integrating GWAS with the high-resolution chromosome conformation capture (Hi-C) data for breast and prostate cancers. We show that more genetic variants map to regulatory elements through the 3D genome structure than the 1D linear genome lacking physical chromatin interactions. Importantly, the association of enhancers, transcription factors, and their target genes with breast and prostate cancers tends to be higher when these regulatory elements are mapped to high-risk SNPs through spatial interactions compared to simply using a linear proximity. Finally, we demonstrate that topologically associating domains (TADs) carrying high-risk SNPs also contain gene regulatory elements whose association with cancer is generally higher than those belonging to control TADs containing no high-risk variants.Conclusions: Our results suggest that many SNPs may contribute to the cancer development by affecting the expression of certain tumor-related genes through long-range chromatin interactions with gene regulatory elements. Integrating large-scale genetic datasets with the 3D genome structure offers an attractive and unique approach to systematically investigate the functional mechanisms of genetic variants in disease risk and progression.

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Constricted migration is associated with stable 3D genome structure differences in melanoma cells

10.1101/856583 ◽

2019 ◽

Cited By ~ 1

Author(s):

Rosela Golloshi ◽

Trevor F. Freeman ◽

Priyojit Das ◽

Thomas Isaac Raines ◽

Rebeca San Martin ◽

...

Keyword(s):

Chromosome Structure ◽

Metastatic Cancer ◽

Genome Structure ◽

Collagen Matrix ◽

Phenotypic Differences ◽

3D Genome ◽

Expression Of Genes ◽

Structure Changes ◽

3D Genome Structure ◽

Nuclear Deformations

AbstractTo spread from a localized tumor, metastatic cancer cells must squeeze through constrictions that cause major nuclear deformations. Since chromosome structure affects nucleus stiffness, gene regulation and DNA repair, here we investigate how confined migration affects or is affected by 3D genome structure. Using melanoma (A375) cells, we identify phenotypic differences in cells that have undergone multiple rounds of constricted migration. These cells display a stably higher migration efficiency, elongated morphology, and differences in the distribution of Lamin A/C and heterochromatin. Using Hi-C, we observe differences in chromosome spatial compartmentalization specific to cells that have passed through constrictions and related alterations in expression of genes associated with migration and metastasis. These sequentially constricted cells also show more nuclear deformations and altered behavior in a 3D collagen matrix. Our observations reveal a relationship between chromosome structure changes, metastatic gene signatures, and the altered nuclear appearance of aggressive melanoma.

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Experience-independent transformation of single-cell 3D genome structure and transcriptome during postnatal development of the mammalian brain

10.1101/2020.04.02.022657 ◽

2020 ◽

Author(s):

Longzhi Tan ◽

Wenping Ma ◽

Honggui Wu ◽

Yinghui Zheng ◽

Dong Xing ◽

...

Keyword(s):

Gene Expression ◽

Single Cell ◽

Genome Structure ◽

Sensory Experience ◽

Mammalian Genome ◽

Brain Cells ◽

List Type ◽

3D Genome ◽

Allele Specific ◽

3D Genome Structure

SUMMARYBoth transcription and 3D organization of the mammalian genome play critical roles in neurodevelopment and its disorders. However, 3D genome structures of single brain cells have not been solved; little is known about the dynamics of single-cell transcriptome and 3D genome after birth. Here we generate a transcriptome atlas of 3,517 cells and a 3D genome atlas of 3,646 cells from the developing mouse cortex and hippocampus, using our high-resolution MALBAC-DT and Dip-C methods. In adults, 3D genome “structure types” delineate all major cell types, with high correlation between A/B compartments and gene expression. During development, both transcriptome and 3D genome are extensively transformed in the first postnatal month. In neurons, 3D genome is rewired across multiple scales, correlated with gene expression modules and independent of sensory experience. Finally, we examine allele-specific structure of imprinted genes, revealing local and chromosome-wide differences. These findings uncover a previously unknown dimension of neurodevelopment.HIGHLIGHTSTranscriptomes and 3D genome structures of single brain cells (both neurons and glia) in the developing mouse forebrainCell type identity encoded in the 3D wiring of the mammalian genome (“structure types”)Major transformation of both transcriptome and 3D genome during the first month of life, independent of sensory experienceAllele-specific 3D structure at 7 imprinted gene loci, including one that spans a whole chromosome

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Radiation-induced DNA damage and repair effects on 3D genome organization

Nature Communications ◽

10.1038/s41467-020-20047-w ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Jacob T. Sanders ◽

Trevor F. Freeman ◽

Yang Xu ◽

Rosela Golloshi ◽

Mary A. Stallard ◽

...

Keyword(s):

Dna Damage ◽

Gene Expression Regulation ◽

Genome Structure ◽

Cell Types ◽

Dimensional Structure ◽

X Rays ◽

3D Genome ◽

Radiation Induced ◽

The Impact ◽

3D Genome Structure

AbstractThe three-dimensional structure of chromosomes plays an important role in gene expression regulation and also influences the repair of radiation-induced DNA damage. Genomic aberrations that disrupt chromosome spatial domains can lead to diseases including cancer, but how the 3D genome structure responds to DNA damage is poorly understood. Here, we investigate the impact of DNA damage response and repair on 3D genome folding using Hi-C experiments on wild type cells and ataxia telangiectasia mutated (ATM) patient cells. We irradiate fibroblasts, lymphoblasts, and ATM-deficient fibroblasts with 5 Gy X-rays and perform Hi-C at 30 minutes, 24 hours, or 5 days after irradiation. We observe that 3D genome changes after irradiation are cell type-specific, with lymphoblastoid cells generally showing more contact changes than irradiated fibroblasts. However, all tested repair-proficient cell types exhibit an increased segregation of topologically associating domains (TADs). This TAD boundary strengthening after irradiation is not observed in ATM deficient fibroblasts and may indicate the presence of a mechanism to protect 3D genome structure integrity during DNA damage repair.

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Subtype-specific epigenomic landscape and 3D genome structure in bladder cancer

10.1101/2020.02.26.966697 ◽

2020 ◽

Author(s):

Tejaswi Iyyanki ◽

Baozhen Zhang ◽

Qiushi Jin ◽

Hongbo Yang ◽

Tingting Liu ◽

...

Keyword(s):

Bladder Cancer ◽

Cancer Cell ◽

Genome Structure ◽

Epigenetic Mechanism ◽

Open Chromatin ◽

3D Genome ◽

Genome Wide ◽

Specific Regulation ◽

And Migration ◽

3D Genome Structure

AbstractMuscle-invasive bladder cancers have recently been characterized by their distinct expression of luminal and basal genes, which could be used to predict key clinical features such as disease progression and overall survival. For example, FOXA1, GATA3, and PPARG have been shown to be essential for luminal subtype-specific regulation and subtype switching, while TP63 and STAT3 are critical for basal subtype bladder cancer. Despite these advances, the underlying epigenetic mechanism and 3D chromatin architecture for subtype-specific regulation in bladder cancers remains largely unknown. Here, we determined the genome-wide transcriptome, enhancer landscape, TF binding profiles (FOXA1 and GATA3) in luminal and basal subtypes of bladder cancers. Furthermore, we mapped genome-wide chromatin interactions by Hi-C in both bladder cancer cell lines and primary patient tumors, for the first time in bladder cancer. We showed that subtype-specific transcription is accompanied by specific open chromatin and epigenomic marks, at least partially driven by distinct TF binding at distal-enhancers of luminal and basal bladder cancers. Finally, we identified a novel clinically relevant transcriptional factor, Neuronal PAS Domain Protein 2 (NPAS2), in luminal bladder cancers that regulates other luminal-specific genes (such as FOXA1, GATA3, and PPARG) and affects cancer cell proliferation and migration. In summary, our work shows a subtype-specific epigenomic and 3D genome structure in urinary bladder cancers and suggested a novel link between the circadian TF NPAS2 and a clinical bladder cancer subtype.

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Exploring the effects of genetic variation on gene regulation in cancer in the context of 3D genome structure

10.1101/2020.10.06.328567 ◽

2020 ◽

Author(s):

Noha Osman ◽

Michal Brylinski

Keyword(s):

High Risk ◽

Genetic Variants ◽

Large Scale ◽

Target Genes ◽

Genome Structure ◽

Regulatory Elements ◽

3D Genome ◽

Risk Snps ◽

Prostate Cancers ◽

3D Genome Structure

AbstractNumerous genome-wide association studies (GWAS) conducted to date revealed genetic variants associated with various diseases, including breast and prostate cancers. Despite the availability of these large-scale data, relatively few variants have been functionally characterized, mainly because the majority of single-nucleotide polymorphisms (SNPs) map to the non-coding regions of the human genome. The functional characterization of these non-coding variants and the identification of their target genes remain challenging. In this communication, we explore the potential functional mechanisms of non-coding SNPs by integrating GWAS with the high-resolution chromosome conformation capture (Hi-C) data for breast and prostate cancers. We show that more genetic variants map to regulatory elements through the 3D genome structure than the 1D linear genome lacking physical chromatin interactions. Importantly, the association of enhancers, transcription factors, and their target genes with breast and prostate cancers tends to be higher when these regulatory elements are mapped to high-risk SNPs through spatial interactions compared to simply using a linear proximity. Finally, we demonstrate that topologically associating domains (TADs) carrying high-risk SNPs also contain gene regulatory elements whose association with cancer is generally higher than those belonging to control TADs containing no high-risk variants. Our results suggest that many SNPs may contribute to the cancer development by affecting the expression of certain tumor-related genes through long-range chromatin interactions with gene regulatory elements. Integrating large-scale genetic datasets with the 3D genome structure offers an attractive and unique approach to systematically investigate the functional mechanisms of genetic variants in disease risk and progression.

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Mining 3D genome structure populations identifies major factors governing the stability of regulatory communities

Nature Communications ◽

10.1038/ncomms11549 ◽

2016 ◽

Vol 7 (1) ◽

Cited By ~ 26

Author(s):

Chao Dai ◽

Wenyuan Li ◽

Harianto Tjong ◽

Shengli Hao ◽

Yonggang Zhou ◽

...

Keyword(s):

Transcription Factor ◽

Genome Structure ◽

Protein Structures ◽

Three Dimensional ◽

Expression Variability ◽

3D Genome ◽

Significant Challenge ◽

The Stability ◽

Major Factors ◽

3D Genome Structure

Abstract Three-dimensional (3D) genome structures vary from cell to cell even in an isogenic sample. Unlike protein structures, genome structures are highly plastic, posing a significant challenge for structure-function mapping. Here we report an approach to comprehensively identify 3D chromatin clusters that each occurs frequently across a population of genome structures, either deconvoluted from ensemble-averaged Hi-C data or from a collection of single-cell Hi-C data. Applying our method to a population of genome structures (at the macrodomain resolution) of lymphoblastoid cells, we identify an atlas of stable inter-chromosomal chromatin clusters. A large number of these clusters are enriched in binding of specific regulatory factors and are therefore defined as ‘Regulatory Communities.’ We reveal two major factors, centromere clustering and transcription factor binding, which significantly stabilize such communities. Finally, we show that the regulatory communities differ substantially from cell to cell, indicating that expression variability could be impacted by genome structures.

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