scholarly journals Identification of chromatin loops from Hi-C interaction matrices by CTCF-CTCF topology classification

2020 ◽  
Author(s):  
Silvia Galan ◽  
François Serra ◽  
Marc A. Marti-Renom
Keyword(s):  
De Novo ◽  
Topological Classification ◽  
Feature Maps ◽  
Chromatin Loops ◽  
Chromatin Interactions ◽  
Pairwise Interactions ◽  
Genome Wide ◽  
Long Range Interactions ◽  
And Function ◽  
Interaction Matrices

ABSTRACTGenome-wide profiling of long-range interactions has revealed that the CCCTC-Binding factor (CTCF) often anchors chromatin loops and is enriched at boundaries of the so-called Topologically Associating Domains or TADs, which suggests that CTCF is essential in the 3D organization of chromatin. However, the systematic topological classification of pairwise CTCF-CTCF interactions has not been yet explored.Here, we developed a computational pipeline able to classify all CTCF-CTCF pairs according to their chromatin interactions from Hi-C experiments. The interaction profiles of all CTCF-CTCF pairs were further structurally clustered using Self-Organizing Feature Maps (SOFM) and their functionality characterized by their epigenetic states. The resulting cluster were then input to a convolutional neural network aiming at the de novo detecting chromatin loops from Hi-C interaction matrices.Our new method, called LOOPbit, is able to automatically detect higher number of pairwise interactions with functional significance compared to other loop callers highlighting the link between chromatin structure and function.

scholarly journals Predicting CTCF-mediated chromatin interactions by integrating genomic and epigenomic features

2017 ◽  
Author(s):  
Yan Kai ◽  
Jaclyn Andricovich ◽  
Zhouhao Zeng ◽  
Jun Zhu ◽  
Alexandros Tzatsos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Long Range ◽  
Zinc Finger Protein ◽  
Cell Types ◽  
Learning Framework ◽  
Chromatin Interactions ◽  
Long Range Interactions ◽  
Extensive Cell ◽  
Cell Type Specific ◽  
And Function

AbstractThe CCCTC-binding zinc finger protein (CTCF)-mediated network of long-range chromatin interactions is important for genome organization and function. Although this network has been considered largely invariant, we found that it exhibits extensive cell-type-specific interactions that contribute to cell identity. Here we present Lollipop—a machine-learning framework—which predicts CTCF-mediated long-range interactions using genomic and epigenomic features. Using ChIA-PET data as benchmark, we demonstrated that Lollipop accurately predicts CTCF-mediated chromatin interactions both within and across cell-types, and outperforms other methods based only on CTCF motif orientation. Predictions were confirmed computationally and experimentally by Chromatin Conformation Capture (3C). Moreover, our approach reveals novel determinants of CTCF-mediated chromatin wiring, such as gene expression within the loops. Our study contributes to a better understanding about the underlying principles of CTCF-mediated chromatin interactions and their impact on gene expression.

scholarly journals HiCORE: Hi-C analysis for identification of core chromatin loops with higher resolution and reliability

2020 ◽  
Author(s):  
Hongwoo Lee ◽  
Pil Joon Seo
Keyword(s):  
High Resolution ◽  
High Throughput Sequencing ◽  
Stochastic Noise ◽  
3D Interaction ◽  
Chromosome Conformation ◽  
Genome Coverage ◽  
Chromatin Loops ◽  
Chromatin Interactions ◽  
Genome Wide ◽  
Physical Interactions

AbstractGenome-wide chromosome conformation capture (3C)-based high-throughput sequencing (Hi-C) has enabled identification of genome-wide chromatin loops. Because the Hi-C map with restriction fragment resolution is intrinsically associated with sparsity and stochastic noise, Hi-C data are usually binned at particular intervals; however, the binning method has limited reliability, especially at high resolution. Here, we describe a new method called HiCORE, which provides simple pipelines and algorithms to overcome the limitations of single-layered binning and predict core chromatin regions with 3D physical interactions. In this approach, multiple layers of binning with slightly shifted genome coverage are generated, and interacting bins at each layer are integrated to infer narrower regions of chromatin interactions. HiCORE predicts chromatin looping regions with higher resolution and contributes to the identification of the precise positions of potential genomic elements.Author SummaryThe Hi-C analysis has enabled to obtain information on 3D interaction of genomes. While various approaches have been developed for the identification of reliable chromatin loops, binning methods have been limitedly improved. We here developed HiCORE algorithm that generates multiple layers of bin-array and specifies core chromatin regions with 3D interactions. We validated our algorithm and provided advantages over conventional binning method. Overall, HiCORE facilitates to predict chromatin loops with higher resolution and reliability, which is particularly relevant in analysis of small genomes.

scholarly journals Gene neighbourhood integrity disrupted by CTCF loss in vivo

2017 ◽  
Author(s):  
Dominic Paul Lee ◽  
Wilson Lek Wen Tan ◽  
Chukwuemeka George Anene-Nzelu ◽  
Peter Yiqing Li ◽  
Tuan Anh Luu Danh ◽  
...  
Keyword(s):  
Large Scale ◽  
De Novo ◽  
Extrusion Process ◽  
Mammalian Genome ◽  
Ctcf Binding ◽  
Ctcf Binding Site ◽  
Loop Formation ◽  
Chromatin Loops ◽  
Genome Wide

The mammalian genome is coiled, compacted and compartmentalized into complex non-random three-dimensional chromatin loops in the nucleus1–3. At the core of chromatin loop formation is CCCTC-binding factor (CTCF), also described as a “weaver of the genome”45. Anchored by CTCF, chromatin loops are proposed to form through a loop extrusion process6, organising themselves into gene neighbourhoods2 that harbour insulated enhancer-promoter domains, restricting enhancer activities to genes within loops, and insulating genes from promiscuous interactions outside of loops2,7–9. Studies targeting CTCF binding site deletions at gene neighbourhood boundaries result in localised gene expression dysregulation8,10–12, and global CTCF depletion recently showed CTCF to be crucial for higher hierarchical chromatin organisation of topologically associating domains (TADs)13. However, the role for CTCF in maintaining sub-TAD CTCF gene neighbourhoods and how gene transcription is affected by CTCF loss remains unclear. In particular, how CTCF gene neighbourhoods govern genome-wide enhancer-promoter interactions require clarification. Here, we took an in vivo approach to assess the global dissolution of CTCF anchored structures in mouse cardiomyocyte-specific Ctcf-knockout (Ctcf-KO), and uncovered large-scale ectopic de novo Enhancer-Promoter (E-P) interactions. In vivo cardiomyocyte-specific Ctcf-KO leads to a heart failure phenotype14, but our analysis integrates genome-wide transcription dysregulation with aberrant E-P interactions in context of CTCF-loop structures, identifying how genes engage their E-P interactions, requiring CTCF looping for their maintenance. Our study points to a mammalian genome that possesses a strong propensity towards spontaneous E-P interactions in vivo, resulting in a diseased transcriptional state, manifest as organ failure. This work solidifies the role of CTCF as the central player for specifying global E-P connections.

scholarly journals Phylogenomics reveals the evolutionary origin of lichenization in chlorophyte algae

2022 ◽  
Author(s):  
Jean Keller ◽  
Camille Puginier ◽  
Cyril Libourel ◽  
Juergen Otte ◽  
Pavel Skaloud ◽  
...  
Keyword(s):  
Green Algae ◽  
Cell Walls ◽  
De Novo ◽  
Glycosyl Hydrolase ◽  
Gene Families ◽  
Major Transitions ◽  
Genome Wide ◽  
Evolution Of Life ◽  
Terrestrial Habitats ◽  
And Function

Mutualistic symbioses, such as lichens formed between fungi and green algae or cyanobacteria, have contributed to major transitions in the evolution of life and are at the center of extant ecosystems. However, our understanding of their evolution and function remains elusive in most cases. Here, we investigated the evolutionary history and the molecular innovations at the origin of lichens in green algae. We de novo sequenced the genomes or transcriptomes of 15 lichen-forming and closely-related non-lichen-forming algae and performed comparative phylogenomics with 22 genomes previously generated. We identified more than 350 functional categories significantly enriched in chlorophyte green algae able to form lichens. Among them, functions such as light perception or resistance to dehydration were shared between lichenizing and other terrestrial algae but lost in non-terrestrial ones, indicating that the ability to live in terrestrial habitats is a prerequisite for lichens to evolve. We detected lichen-specific expansions of glycosyl hydrolase gene families known to remodel cell walls, including the glycosyl hydrolase 8 which was acquired in lichenizing Trebouxiophyceae by horizontal gene transfer from bacteria, concomitantly with the ability to form lichens. Mining genome-wide orthogroups, we found additional evidence supporting at least two independent origins of lichen-forming ability in chlorophyte green algae. We conclude that the lichen-forming ability evolved multiple times in chlorophyte green algae, following a two-step mechanism which involves an ancestral adaptation to terrestrial lifestyle and molecular innovations to modify the partners cell walls.

scholarly journals CTCF, WAPL and PDS5 proteins control the formation of TADs and loops by cohesin

2017 ◽  
Author(s):  
Gordana Wutz ◽  
Csilla Várnai ◽  
Kota Nagasaka ◽  
David A Cisneros ◽  
Roman Stocsits ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Long Range ◽  
Direct Evidence ◽  
Chromatin Loops ◽  
Chromatin Interactions ◽  
Binding Partners ◽  
Topologically Associating Domains ◽  
Genome Wide ◽  
Mammalian Genomes

AbstractMammalian genomes are organized into compartments, topologically-associating domains (TADs) and loops to facilitate gene regulation and other chromosomal functions. Compartments are formed by nucleosomal interactions, but how TADs and loops are generated is unknown. It has been proposed that cohesin forms these structures by extruding loops until it encounters CTCF, but direct evidence for this hypothesis is missing. Here we show that cohesin suppresses compartments but is essential for TADs and loops, that CTCF defines their boundaries, and that WAPL and its PDS5 binding partners control the length of chromatin loops. In the absence of WAPL and PDS5 proteins, cohesin passes CTCF sites with increased frequency, forms extended chromatin loops, accumulates in axial chromosomal positions (vermicelli) and condenses chromosomes to an extent normally only seen in mitosis. These results show that cohesin has an essential genome-wide function in mediating long-range chromatin interactions and support the hypothesis that cohesin creates these by loop extrusion, until it is delayed by CTCF in a manner dependent on PDS5 proteins, or until it is released from DNA by WAPL.

scholarly journals riboCIRC: a comprehensive database of translatable circRNAs

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Huihui Li ◽  
Mingzhe Xie ◽  
Yan Wang ◽  
Ludong Yang ◽  
Zhi Xie ◽  
...  
Keyword(s):  
De Novo ◽  
Species Conservation ◽  
Structure And Function ◽  
Research Community ◽  
Genome Browser ◽  
Valuable Resource ◽  
Sequence Structure ◽  
A Genome ◽  
Context Specific ◽  
And Function

AbstractriboCIRC is a translatome data-oriented circRNA database specifically designed for hosting, exploring, analyzing, and visualizing translatable circRNAs from multi-species. The database provides a comprehensive repository of computationally predicted ribosome-associated circRNAs; a manually curated collection of experimentally verified translated circRNAs; an evaluation of cross-species conservation of translatable circRNAs; a systematic de novo annotation of putative circRNA-encoded peptides, including sequence, structure, and function; and a genome browser to visualize the context-specific occupant footprints of circRNAs. It represents a valuable resource for the circRNA research community and is publicly available at http://www.ribocirc.com.

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