scholarly journals L1 and B1 repeats blueprint the spatial organization of chromatin

2019 ◽  
Author(s):  
J. Yuyang Lu ◽  
Lei Chang ◽  
Tong Li ◽  
Ting Wang ◽  
Yafei Yin ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Mammalian Cells ◽  
Spatial Organization ◽  
Genome Structure ◽  
Three Dimensional ◽  
Order Structure ◽  
Basic Principles ◽  
Heterochromatin Protein ◽  
3D Genome ◽  
Genomic Repeats

SUMMARYDespite extensive mapping of three-dimensional (3D) chromatin structures, the basic principles underlying genome folding remain unknown. Here, we report a fundamental role for L1 and B1 retrotransposons in shaping the macroscopic 3D genome structure. Homotypic clustering of B1 and L1 repeats in the nuclear interior or at the nuclear and nucleolar peripheries, respectively, segregates the genome into mutually exclusive nuclear compartments. This spatial segregation of L1 and B1 is conserved in mouse and human cells, and occurs dynamically during establishment of the 3D chromatin structure in early embryogenesis and the cell cycle. Depletion of L1 transcripts drastically disrupts the spatial distributions of L1- and B1-rich compartments. L1 transcripts are strongly associated with L1 DNA sequences and induce phase separation of the heterochromatin protein HP1α. Our results suggest that genomic repeats act as the blueprint of chromatin macrostructure, thus explaining the conserved higher-order structure of chromatin across mammalian cells.

The 3D Genome Structure of Single Cells

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Tianming Zhou ◽  
Ruochi Zhang ◽  
Jian Ma
Keyword(s):  
Single Cell ◽  
Data Science ◽  
Spatial Organization ◽  
Method Development ◽  
Single Cells ◽  
Genome Structure ◽  
Computational Method ◽  
Publication Date ◽  
3D Genome ◽  
Genome Features

The spatial organization of the genome in the cell nucleus is pivotal to cell function. However, how the 3D genome organization and its dynamics influence cellular phenotypes remains poorly understood. The very recent development of single-cell technologies for probing the 3D genome, especially single-cell Hi-C (scHi-C), has ushered in a new era of unveiling cell-to-cell variability of 3D genome features at an unprecedented resolution. Here, we review recent developments in computational approaches to the analysis of scHi-C, including data processing, dimensionality reduction, imputation for enhancing data quality, and the revealing of 3D genome features at single-cell resolution. While much progress has been made in computational method development to analyze single-cell 3D genomes, substantial future work is needed to improve data interpretation and multimodal data integration, which are critical to reveal fundamental connections between genome structure and function among heterogeneous cell populations in various biological contexts. Expected final online publication date for the Annual Review of Biomedical Data Science, Volume 4 is July 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Repeat elements organize 3D genome structure and mediate transcription in the filamentous fungusEpichloë festucae

2018 ◽  
Author(s):  
David J Winter ◽  
Austen RD Ganley ◽  
Carolyn A Young ◽  
Ivan Liachko ◽  
Christopher L Schardl ◽  
...  
Keyword(s):  
Genome Structure ◽  
Regulation Of Gene Expression ◽  
Three Dimensional ◽  
Structural Features ◽  
Dimensional Structure ◽  
In Planta ◽  
Repeat Elements ◽  
Symbiotic Relationships ◽  
3D Genome ◽  
Transcriptional Changes

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.

scholarly journals Spatial organization of DNA sequences directs the assembly of bacterial chromatin by a nucleoid-associated protein

2017 ◽  
Vol 292 (18) ◽  
pp. 7607-7618 ◽  
Author(s):  
Aleksandre Japaridze ◽  
Sylvain Renevey ◽  
Patrick Sobetzko ◽  
Liubov Stoliar ◽  
William Nasser ◽  
...  
Keyword(s):  
Long Range ◽  
Dna Sequence ◽  
Dna Sequences ◽  
Spatial Organization ◽  
Three Dimensional ◽  
Sequence Motif ◽  
Structural Differentiation ◽  
Ample Evidence ◽  
Organizational Principle ◽  
Nucleoprotein Complexes

Structural differentiation of bacterial chromatin depends on cooperative binding of abundant nucleoid-associated proteins at numerous genomic DNA sites and stabilization of distinct long-range nucleoprotein structures. Histone-like nucleoid-structuring protein (H-NS) is an abundant DNA-bridging, nucleoid-associated protein that binds to an AT-rich conserved DNA sequence motif and regulates both the shape and the genetic expression of the bacterial chromosome. Although there is ample evidence that the mode of H-NS binding depends on environmental conditions, the role of the spatial organization of H-NS-binding sequences in the assembly of long-range nucleoprotein structures remains unknown. In this study, by using high-resolution atomic force microscopy combined with biochemical assays, we explored the formation of H-NS nucleoprotein complexes on circular DNA molecules having different arrangements of identical sequences containing high-affinity H-NS-binding sites. We provide the first experimental evidence that variable sequence arrangements result in various three-dimensional nucleoprotein structures that differ in their shape and the capacity to constrain supercoils and compact the DNA. We believe that the DNA sequence-directed versatile assembly of periodic higher-order structures reveals a general organizational principle that can be exploited for knowledge-based design of long-range nucleoprotein complexes and purposeful manipulation of the bacterial chromatin architecture.

scholarly journals The role of CTCF in regulating nuclear organization

2008 ◽  
Vol 205 (4) ◽  
pp. 747-750 ◽  
Author(s):  
Adam Williams ◽  
Richard A. Flavell
Keyword(s):  
Long Range ◽  
Dna Sequences ◽  
Spatial Organization ◽  
Zinc Finger Protein ◽  
Nuclear Organization ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Binding Factor ◽  
Long Range Interactions ◽  
Regulatory Functions

The spatial organization of the genome is thought to play an important part in the coordination of gene regulation. New techniques have been used to identify specific long-range interactions between distal DNA sequences, revealing an ever-increasing complexity to nuclear organization. CCCTC-binding factor (CTCF) is a versatile zinc finger protein with diverse regulatory functions. New data now help define how CTCF mediates both long-range intrachromosomal and interchromosomal interactions, and highlight CTCF as an important factor in determining the three-dimensional structure of the genome.

scholarly journals PGS: a dynamic and automated population-based genome structure software

2017 ◽  
Author(s):  
Nan Hua ◽  
Harianto Tjong ◽  
Hanjun Shin ◽  
Ke Gong ◽  
Xianghong Jasmine Zhou ◽  
...  
Keyword(s):  
High Performance ◽  
Spatial Organization ◽  
Genome Structure ◽  
Probabilistic Approach ◽  
Population Based ◽  
Chromatin Interaction ◽  
3D Analysis ◽  
3D Genome ◽  
A Genome ◽  
Contact Frequency

ABSTRACTHi-C technologies are widely used to investigate the spatial organization of genomes. However, the structural variability of the genome is a great challenge to interpreting ensemble-averaged Hi-C data, particularly for long-range/interchromosomal interactions. We pioneered a probabilistic approach for generating a population of distinct diploid 3D genome structures consistent with all the chromatin-chromatin interaction probabilities from Hi-C experiments. Each structure in the population is a physical model of the genome in 3D. Analysis of these models yields new insights into the causes and the functional properties of the genome’s organization in space and time. We provide a user-friendly software package, called PGS, that runs on local machines and high-performance computing platforms. PGS takes a genome-wide Hi-C contact frequency matrix and produces an ensemble of 3D genome structures entirely consistent with the input. The software automatically generates an analysis report, and also provides tools to extract and analyze the 3D coordinates of specific domains.

scholarly journals Chromatin spatial organization of wild type and mutant peanuts reveals high-resolution genomic architecture and interaction alterations

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Xingguo Zhang ◽  
Manish K. Pandey ◽  
Jianping Wang ◽  
Kunkun Zhao ◽  
Xingli Ma ◽  
...  
Keyword(s):  
Spatial Organization ◽  
Gene Expression Regulation ◽  
Three Dimensional ◽  
Active Regions ◽  
Mutant Line ◽  
Binding Motif ◽  
Wild Type ◽  
3D Genome ◽  
Topologically Associated Domains ◽  
High Gene

Abstract Background Three-dimensional (3D) chromatin organization provides a critical foundation to investigate gene expression regulation and cellular homeostasis. Results Here, we present the first 3D genome architecture maps in wild type and mutant allotetraploid peanut lines, which illustrate A/B compartments, topologically associated domains (TADs), and widespread chromatin interactions. Most peanut chromosomal arms (52.3%) have active regions (A compartments) with relatively high gene density and high transcriptional levels. About 2.0% of chromosomal regions switch from inactive to active (B-to-A) in the mutant line, harboring 58 differentially expressed genes enriched in flavonoid biosynthesis and circadian rhythm functions. The mutant peanut line shows a higher number of genome-wide cis-interactions than its wild-type. The present study reveals a new TAD in the mutant line that generates different chromatin loops and harbors a specific upstream AP2EREBP-binding motif which might upregulate the expression of the GA2ox gene and decrease active gibberellin (GA) content, presumably making the mutant plant dwarf. Conclusions Our findings will shed new light on the relationship between 3D chromatin architecture and transcriptional regulation in plants.

scholarly journals GEM: A manifold learning based framework for reconstructing spatial organizations of chromosomes

2017 ◽  
Author(s):  
Guangxiang Zhu ◽  
Wenxuan Deng ◽  
Hailin Hu ◽  
Rui Ma ◽  
Sai Zhang ◽  
...  
Keyword(s):  
Manifold Learning ◽  
Learning Strategy ◽  
Genome Structure ◽  
Three Dimensional ◽  
Conformational Energy ◽  
3D Genome ◽  
Learning Framework ◽  
Reconstruction Methods ◽  
Eukaryotic Gene ◽  
Validation Tests

AbstractDecoding the spatial organizations of chromosomes has crucial implications for studying eukaryotic gene regulation. Recently, Chromosomal conformation capture based technologies, such as Hi-C, have been widely used to uncover the interaction frequencies of genomic loci in high-throughput and genome-wide manner and provide new insights into the folding of three-dimensional (3D) genome structure. In this paper, we develop a novel manifold learning framework, called GEM (Genomic organization reconstructor based on conformational Energy and Manifold learning), to elucidate the underlying 3D spatial organizations of chromosomes from Hi-C data. Unlike previous chromatin structure reconstruction methods, which explicitly assume specific relationships between Hi-C interaction frequencies and spatial distances between distal genomic loci, GEM is able to reconstruct an ensemble of chromatin conformations by directly embedding the neigh-boring affinities from Hi-C space into 3D Euclidean space based on a manifold learning strategy that considers both the fitness of Hi-C data and the biophysical feasibility of the modeled structures, which are measured by the conformational energy derived from our current biophysical knowledge about the 3D polymer model. Extensive validation tests on both simulated interaction frequency data and experimental Hi-C data of yeast and human demonstrated that GEM not only greatly outperformed other state-of-art modeling methods but also reconstructed accurate chromatin structures that agreed well with the hold-out or independent Hi-C data and sparse geometric restraints derived from the previous fluorescence in situ hybridization (FISH) studies. In addition, as GEM can generate accurate spatial organizations of chromosomes by integrating both experimentally-derived spatial contacts and conformational energy, we for the first time extended our modeling method to recover long-range genomic interactions that are missing from the original Hi-C data. All these results indicated that GEM can provide a physically and physiologically valid 3D representations of the organizations of chromosomes and thus serve as an effective and useful genome structure reconstructor.

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

2017 ◽  
Author(s):  
Fidel Ramírez ◽  
Vivek Bhardwaj ◽  
José Villaveces ◽  
Laura Arrigoni ◽  
Björn A. Grüning ◽  
...  
Keyword(s):  
High Resolution ◽  
Dna Sequences ◽  
Spatial Organization ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Open Chromatin ◽  
Promoter Regions ◽  
Dna Motifs ◽  
3D Genome ◽  
Eukaryotic Chromatin

AbstractEukaryotic chromatin is partitioned into domains called TADs that are broadly conserved between species and virtually identical among cell types within the same species. Previous studies in mammals have shown that the DNA binding protein CTCF and cohesin contribute to a fraction of TAD boundaries. Apart from this, the molecular mechanisms governing this partitioning remain poorly understood. Using our new software, HiCExplorer, we annotated high-resolution (570 bp) TAD boundaries in flies and identified eight DNA motifs enriched at boundaries. Known insulator proteins bind five of these motifs while the remaining three motifs are novel. We find that boundaries are either at core promoters of active genes or at non-promoter regions of inactive chromatin and that these two groups are characterized by different sets of DNA motifs. Most boundaries are present at divergent promoters of constitutively expressed genes and the gene expression tends to be coordinated within TADs. In contrast to mammals, the CTCF motif is only present on 2% of boundaries in flies. We demonstrate that boundaries can be accurately predicted using only the motif sequences, along with open chromatin, suggesting that DNA sequence encodes the 3D genome architecture in flies. Finally, we present an interactive online database to access and explore the spatial organization of fly, mouse and human genomes, available at http://chorogeome.ie-freiburg.mpg.de.

Nuclear long non-coding RNAs as epigenetic regulators in cancer

2021 ◽  
Vol 28 ◽  
Author(s):  
Hiroaki Tachiwana ◽  
Noriko Saitoh
Keyword(s):  
Mammalian Cells ◽  
Genome Structure ◽  
Methyl Transferase ◽  
Cancer Hallmarks ◽  
3D Genome ◽  
Transcription Sites ◽  
Non Coding Rnas ◽  
Epigenetic Regulators ◽  
Nuclear Domains ◽  
In Cis

Background: Transcriptome analyses have revealed the presence of numerous long non-coding RNAs (lncRNAs) in mammalian cells. Many lncRNAs are expressed in development-, differentiation-, and disease-specific manners, suggesting their importance as cell regulators. Some nuclear lncRNAs are bound to specific genomic loci, either near or distant from their own transcription sites, and regulate gene expression in cis or trans. These lncRNAs recruit epigenetic factors, including the DNA methyl transferase and histone modification complex, and mediate both the 3D genome structure and nuclear domains. LncRNAs are now considered as an emerging member of epigenetic regulators. LncRNAs are dysregulated in various types of cancer, and act as either oncogenic or tumor-suppressing factors. They are involved in virtually all of the cancer hallmarks, and are potential diagnostic markers and therapeutic targets. Objective: In this review, we describe several representative lncRNAs and provide a current overview of the mechanisms by which lncRNAs participate in epigenetic regulation and contribute to cancer development.

Chromosome interactome inferred from mitosis-G1 transition

2016 ◽  
Author(s):  
Y.A. Eidelman ◽  
S.V. Slanina ◽  
A.V. Aleshchenko ◽  
S.G. Andreev
Keyword(s):  
Spatial Organization ◽  
Contact Map ◽  
Interphase Chromosome ◽  
Basic Principles ◽  
Chromosome Conformation ◽  
3D Genome ◽  
Contact Patterns ◽  
Genome Wide ◽  
Genome Study ◽  
Contact Data

ABSTRACTThe progress in experimental techniques aimed at 3D genome study is yet to bring about revelation of basic principles of genome folding. Chromosome conformation capture Hi-C technologies provide genome wide mapping of genomic loci interactions but spatial organization of chromosomes remains unknown. Here, we develop a polymer modeling approach to generate the ensemble of 3D chromosome conformations for mapping genetic loci contacts and the positions of megabase chromosomal domains in interphase chromosome at different time of mitosis-interphase transition. We demonstrate that (*) whole chromosome contact map (interactome) generated for mouse chromosome 18 structure and (**) contact patterns, observed soon after mitotic decondensation and remaining similar during G1, correlate well with the experimental Hi-C contact data. The results suggest that contact map formation and spatial compartmentalization of an interphase chromosome are driven by interactions between different types of domains during formation of globular chromosome state at the end of mitotis-G1 transition.

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