scholarly journals Coolpup.py:versatile pile-up analysis of Hi-C data

2019 ◽  
Author(s):  
Ilya M. Flyamer ◽  
Robert S. Illingworth ◽  
Wendy A. Bickmore
Keyword(s):  
Genome Organization ◽  
Source Code ◽  
Computationally Efficient ◽  
3D Genome ◽  
Genome Wide ◽  
Pile Up ◽  
Versatile Tool ◽  
Cross Platform ◽  
Novel Variation

AbstractMotivationHi-C is currently the method of choice to investigate the global 3D organisation of the genome. A major limitation of Hi-C is the sequencing depth required to robustly detect loops in the data. A popular approach used to mitigate this issue, even in single-cell Hi-C data, is genome-wide averaging (piling-up) of peaks, or other features, annotated in high-resolution datasets, to measure their prominence in less deeply sequenced data. However current tools do not provide a computationally efficient and versatile implementation of this approach.ResultsHere we describecoolpup.py– a versatile tool to perform pile-up analysis on Hi-C data. We demonstrate its utility by replicating previously published findings regarding the role of cohesin and CTCF in 3D genome organization, as well as discovering novel details of Polycomb-driven interactions. We also present a novel variation of the pile-up approach that can aid the in statistical analysis of looping interactions. We anticipate thatcoolpup.pywill aid in Hi-C data analysis by allowing easy to use, versatile and efficient generation of pileups.Availability and implementationCoolpup.pyis cross-platform, open-source and free (MIT licensed) software. Source code is available fromhttps://github.com/Phlya/coolpuppyand it can be installed from the Python Packaging [email protected]

scholarly journals Coolpup.py: versatile pile-up analysis of Hi-C data

2020 ◽  
Vol 36 (10) ◽  
pp. 2980-2985 ◽  
Author(s):  
Ilya M Flyamer ◽  
Robert S Illingworth ◽  
Wendy A Bickmore
Keyword(s):  
Genome Organization ◽  
Source Code ◽  
Computationally Efficient ◽  
3D Genome ◽  
Genome Wide ◽  
Pile Up ◽  
Versatile Tool ◽  
Cross Platform ◽  
Novel Variation

Abstract Motivation Hi-C is currently the method of choice to investigate the global 3D organization of the genome. A major limitation of Hi-C is the sequencing depth required to robustly detect loops in the data. A popular approach used to mitigate this issue, even in single-cell Hi-C data, is genome-wide averaging (piling-up) of peaks, or other features, annotated in high-resolution datasets, to measure their prominence in less deeply sequenced data. However, current tools do not provide a computationally efficient and versatile implementation of this approach. Results Here, we describe coolpup.py—a versatile tool to perform pile-up analysis on Hi-C data. We demonstrate its utility by replicating previously published findings regarding the role of cohesin and CTCF in 3D genome organization, as well as discovering novel details of Polycomb-driven interactions. We also present a novel variation of the pile-up approach that can aid the statistical analysis of looping interactions. We anticipate that coolpup.py will aid in Hi-C data analysis by allowing easy to use, versatile and efficient generation of pile-ups. Availability and implementation Coolpup.py is cross-platform, open-source and free (MIT licensed) software. Source code is available from https://github.com/Phlya/coolpuppy and it can be installed from the Python Packaging Index.

scholarly journals Functional correlation of H3K9me2 and nuclear compartment formation

2020 ◽  
Author(s):  
Kei Fukuda ◽  
Chikako Shimura ◽  
Hisashi Miura ◽  
Akie Tanigawa ◽  
Takehiro Suzuki ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Genome Organization ◽  
Mammalian Cells ◽  
Embryonic Stem ◽  
Epigenetic Mark ◽  
3 Dimensional ◽  
3D Genome ◽  
Functional Correlation ◽  
Genome Wide

AbstractBackgroundHistone H3 lysine 9 dimethylation (H3K9me2) is a highly conserved silencing epigenetic mark. Chromatin marked with H3K9me2 forms large domains in mammalian cells and correlates well with lamina-associated domains and the B compartment. However, the role of H3K9me2 in 3-dimensional (3D) genome organization remains unclear.ResultsWe investigated the genome-wide H3K9me2 distribution, the transcriptome and 3D genome organization in mouse embryonic stem cells (mESCs) upon the inhibition or depletion of H3K9 methyltransferases (MTases) G9a/GLP, SETDB1, and SUV39H1/2. We found that H3K9me2 is regulated by these five MTases; however, H3K9me2 and transcription in the A and B compartments were largely regulated by different sets of the MTases: H3K9me2 in the A compartments were mainly regulated by G9a/GLP and SETDB1, while H3K9me2 in the B compartments were regulated by all five H3K9 MTases. Furthermore, decreased H3K9me2 correlated with the changes to the more active compartmental state that accompanied transcriptional activation.ConclusionOur data showed that H3K9me2 domain formation is functionally linked to 3D genome organization.

scholarly journals Regulation of mammalian 3D genome organization and histone H3K9 dimethylation by H3K9 methyltransferases

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Kei Fukuda ◽  
Chikako Shimura ◽  
Hisashi Miura ◽  
Akie Tanigawa ◽  
Takehiro Suzuki ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Genome Organization ◽  
Mammalian Cells ◽  
Embryonic Stem ◽  
Epigenetic Mark ◽  
3 Dimensional ◽  
3D Genome ◽  
Genome Wide ◽  
H3k9 Dimethylation

AbstractHistone H3 lysine 9 dimethylation (H3K9me2) is a highly conserved silencing epigenetic mark. Chromatin marked with H3K9me2 forms large domains in mammalian cells and overlaps well with lamina-associated domains and the B compartment defined by Hi-C. However, the role of H3K9me2 in 3-dimensional (3D) genome organization remains unclear. Here, we investigated genome-wide H3K9me2 distribution, transcriptome, and 3D genome organization in mouse embryonic stem cells following the inhibition or depletion of H3K9 methyltransferases (MTases): G9a, GLP, SETDB1, SUV39H1, and SUV39H2. We show that H3K9me2 is regulated by all five MTases; however, H3K9me2 and transcription in the A and B compartments are regulated by different MTases. H3K9me2 in the A compartments is primarily regulated by G9a/GLP and SETDB1, while H3K9me2 in the B compartments is regulated by all five MTases. Furthermore, decreased H3K9me2 correlates with changes to more active compartmental state that accompanied transcriptional activation. Thus, H3K9me2 contributes to inactive compartment setting.

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

2019 ◽  
Vol 10 (1) ◽  
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.

scholarly journals Contribution of 3D genome topological domains to genetic risk of cancers

2021 ◽  
Author(s):  
Kim Philipp Jablonski ◽  
Leopold Carron ◽  
Julien Mozziconacci ◽  
Thierry Forné ◽  
Marc-Thorsten Hütt ◽  
...  
Keyword(s):  
Genetic Risk ◽  
Genome Organization ◽  
Association Studies ◽  
Embryonic Stem ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Entire Genome ◽  
Topological Domains ◽  
3D Genome ◽  
Genome Wide

Genome-wide association studies have identified statistical associations between various diseases, including cancers, and a large number of single-nucleotide polymorphisms (SNPs). However, they provide no direct explanation of the mechanisms underlying the association. Based on the recent discovery that changes in 3-dimensional genome organization may have functional consequences on gene regulation favoring diseases, we investigated systematically the genome-wide distribution of disease-associated SNPs with respect to a specific feature of 3D genome organization: topologically-associating domains (TADs) and their borders. For each of 449 diseases, we tested whether the associated SNPs are present in TAD borders more often than observed by chance, where chance (i.e. the null model in statistical terms) corresponds to the same number of pointwise loci drawn at random either in the entire genome, or in the entire set of disease-associated SNPs listed in the GWAS catalog. Our analysis shows that a fraction of diseases display such a preferential location of their risk loci. Moreover, cancers are relatively more frequent among these diseases, and this predominance is generally enhanced when considering only intergenic SNPs. The structure of SNP-based diseasome networks confirms that TAD border enrichment in risk loci differ between cancers and non-cancer diseases. Different TAD border enrichments are observed in embryonic stem cells and differentiated cells, which agrees with an evolution along embryogenesis of the 3D genome organization into topological domains. Our results suggest that, for certain diseases, part of the genetic risk lies in a local genetic variation affecting the genome partitioning in topologically-insulated domains. Investigating this possible contribution to genetic risk is particularly relevant in cancers. This study thus opens a way of interpreting genome-wide association studies, by distinguishing two types of disease-associated SNPs: one with a direct effect on an individual gene, the other acting in interplay with 3D genome organization.

scholarly journals Relaxed 3D genome conformation facilitates the pluripotent to totipotent state transition in embryonic stem cells

2020 ◽  
Author(s):  
Jiali Yu ◽  
Yezhang Zhu ◽  
Jiahui Gu ◽  
Chaoran Xue ◽  
Long Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Genome Organization ◽  
Critical Role ◽  
Embryonic Stem ◽  
List Type ◽  
Down Regulation ◽  
Chromatin Loops ◽  
3D Genome

SUMMARYThe 3D genome organization is crucial for gene regulation. Although recent studies have revealed a uniquely relaxed genome conformation in totipotent early blastmeres of both fertilized and cloned embryos, how weakened higher-order chromatin structure is functionally linked to totipotency acquisition remains elusive. Using low-input Hi-C, ATAC-seq, and ChIP-seq, we systematically examined the dynamics of 3D genome and epigenome during pluripotency-to-totipotency transition in mouse embryonic stem cells (ESCs). The totipotent 2-cell-embro-like cells (2CLCs) exhibit more relaxed chromatin architecture compared to ESCs, including global weakening of both enhancer-promoter interactions and TAD insulation. While the former leads to inactivation of ESC enhancers and down-regulation of pluripotent genes, the latter may facilitate contacts between the new enhancers arising in 2CLCs and neighboring 2C genes. Importantly, disruption of chromatin loops by depleting CTCF or cohesin promotes ESC to 2CLC transition. Our results thus establish a critical role of 3D genome organization in totipotency acquisition.HIGHLIGHTSGlobal weakening of the 3D genome conformation during ESC to 2CLC transitionLoss of enhancer-promoter loops and down-regulation of pluripotent genes in 2CLCsInactivation of ESC enhancers and formation of new enhancers in 2CLCsDisruption of chromatin loops by depleting CTCF or cohesin promotes 2CLC emergence

scholarly journals Easy Hi-C: A simple efficient protocol for 3D genome mapping in small cell populations

2018 ◽  
Author(s):  
Leina Lu ◽  
Xiaoxiao Liu ◽  
Jun Peng ◽  
Yan Li ◽  
Fulai Jin
Keyword(s):  
Genome Organization ◽  
Genome Mapping ◽  
Mammalian Genome ◽  
Small Cell ◽  
Genome Architecture ◽  
Enzymatic Reactions ◽  
High Quality ◽  
3D Genome ◽  
Proximity Ligation ◽  
Genome Wide

Despite the growing interest in studying the mammalian genome organization, it is still challenging to map the DNA contacts genome-wide. Here we present easy Hi-C (eHi-C), a highly efficient method for unbiased mapping of 3D genome architecture. The eHi-C protocol only involves a series of enzymatic reactions and maximizes the recovery of DNA products from proximity ligation. We show that eHi-C can be performed with 0.1 million cells and yields high quality libraries comparable to Hi-C.

scholarly journals Role of lamins in 3D genome organization and global gene expression

Nucleus ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 33-41 ◽  
Author(s):  
Youngjo Kim ◽  
Xiaobin Zheng ◽  
Yixian Zheng
Keyword(s):  
Gene Expression ◽  
Genome Organization ◽  
Global Gene Expression ◽  
3D Genome
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