scholarly journals C3D: A tool to predict 3D genomic interactions between cis-regulatory elements

2017 ◽  
Author(s):  
Tahmid Mehdi ◽  
Swneke D. Bailey ◽  
Paul Guilhamon ◽  
Mathieu Lupien
Keyword(s):  
Regulatory Elements ◽  
Gene Promoters ◽  
Cell Type ◽  
Computational Tool ◽  
3D Genome ◽  
Dna Accessibility ◽  
Chromatin Interactions ◽  
Hypersensitive Sites ◽  
R Packages ◽  
Mcf 7

ABSTRACTMotivationThe 3D genome architecture influences the regulation of genes by facilitating chromatin interactions between distal cis-regulatory elements and gene promoters. We implement Cross Cell-type Correlation based on DNA accessibility (C3D), a highly customizable computational tool that predicts chromatin interactions using an unsupervised algorithm that utilizes correlations in chromatin measurements, such as DNaseI hypersensitivity signals.ResultsC3D accurately predicts 32.7%, 18.3% and 24.1% of interactions, validated by ChIA-PET assays, between promoters and distal regions that overlie DNaseI hypersensitive sites in K562, MCF-7 and GM12878 cells, respectively.AvailabilitySource code is open-source and freely available on GitHub (https://github.com/LupienLabOrganization/C3D) under the GNU GPLv3 license. C3D is implemented in Bash and R; it runs on any platform with Bash (≥4.0), R (≥3.1.1) and BEDTools (≥2.19.0). It requires the following R packages: GenomicRanges, Sushi, data.table, preprocessCore and dynamicTreeCut.

scholarly journals Single-cell-resolved dynamics of chromatin architecture delineate cell and regulatory states in wildtype and cloche/npas4l mutant zebrafish embryos

2020 ◽  
Author(s):  
Alison C. McGarvey ◽  
Wolfgang Kopp ◽  
Dubravka Vučićević ◽  
Rieke Kempfer ◽  
Kenny Mattonet ◽  
...  
Keyword(s):  
Single Cell ◽  
Transcriptional Activity ◽  
Regulatory Elements ◽  
Zebrafish Embryos ◽  
Computational Tool ◽  
Post Translational Modifications ◽  
Future Studies ◽  
3D Genome ◽  
Dna Accessibility ◽  
Intricate Mechanism

DNA accessibility of cis regulatory elements (CREs) dictates transcriptional activity and drives cell differentiation during development. While many of the genes that regulate embryonic development have been described, the underlying CRE dynamics controlling their expression remain largely unknown. To address this, we applied single-cell combinatorial indexing ATAC-seq (sci-ATAC-seq) to whole 24 hours post fertilization (hpf) stage zebrafish embryos and developed a new computational tool, ScregSeg, that selects informative genome segments and classifies complex accessibility dynamics. We integrated the ScregSeg output with bulk measurements for histone post-translational modifications and 3D genome organization, expanding knowledge of regulatory principles between chromatin modalities. Sci-ATAC-seq profiling of npas4l/cloche mutant embryos revealed novel cellular roles for this hemato-vascular transcriptional master regulator and suggests an intricate mechanism regulating its expression. Our work constitutes a valuable resource for future studies in developmental, molecular, and computational biology.

scholarly journals The 3D Genome Browser: a web-based browser for visualizing 3D genome organization and long-range chromatin interactions

2017 ◽  
Author(s):  
Yanli Wang ◽  
Bo Zhang ◽  
Lijun Zhang ◽  
Lin An ◽  
Jie Xu ◽  
...  
Keyword(s):  
Genome Organization ◽  
Target Genes ◽  
Genome Structure ◽  
Regulatory Elements ◽  
Genomic Region ◽  
Genome Browser ◽  
Chromatin Interaction ◽  
Interaction Data ◽  
3D Genome ◽  
Chromatin Interactions

ABSTRACTRecent advent of 3C-based technologies such as Hi-C and ChIA-PET provides us an opportunity to explore chromatin interactions and 3D genome organization in an unprecedented scale and resolution. However, it remains a challenge to visualize chromatin interaction data due to its size and complexity. Here, we introduce the 3D Genome Browser (http://3dgenome.org), which allows users to conveniently explore both publicly available and their own chromatin interaction data. Users can also seamlessly integrate other “omics” data sets, such as ChIP-Seq and RNA-Seq for the same genomic region, to gain a complete view of both regulatory landscape and 3D genome structure for any given gene. Finally, our browser provides multiple methods to link distal cis-regulatory elements with their potential target genes, including virtual 4C, ChIA-PET, Capture Hi-C and cross-cell-type correlation of proximal and distal DNA hypersensitive sites, and therefore represents a valuable resource for the study of gene regulation in mammalian genomes.

scholarly journals A revised model for promoter competition based on multi-way chromatin interactions at the α-globin locus

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
A. Marieke Oudelaar ◽  
Caroline L. Harrold ◽  
Lars L. P. Hanssen ◽  
Jelena M. Telenius ◽  
Douglas R. Higgs ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Regulation Of Gene Expression ◽  
Regulatory Elements ◽  
Chromatin Domain ◽  
Gene Promoters ◽  
Multiple Promoters ◽  
Chromatin Interactions ◽  
Technological Advances ◽  
Single Complex ◽  
Membrane Bound

AbstractSpecific communication between gene promoters and enhancers is critical for accurate regulation of gene expression. However, it remains unclear how specific interactions between multiple regulatory elements contained within a single chromatin domain are coordinated. Recent technological advances which can detect multi-way chromatin interactions at single alleles can provide insights into how multiple regulatory elements cooperate or compete for transcriptional activation. Here, we use such an approach to investigate how interactions of the α-globin enhancers are distributed between multiple promoters in a mouse model in which the α-globin domain is extended to include several additional genes. Our data show that gene promoters do not form mutually exclusive interactions with enhancers, but all interact simultaneously in a single complex. These findings suggest that promoters do not structurally compete for interactions with enhancers, but form a regulatory hub structure, which is consistent with recent models of transcriptional activation occurring in non-membrane bound nuclear compartments.

scholarly journals Distinct roles for CDK-Mediator in controlling Polycomb-dependent chromosomal interactions and priming genes for induction

2021 ◽  
Author(s):  
Emilia Dimitrova ◽  
Angelika Feldmann ◽  
Robin H van der Weide ◽  
Koen D Flach ◽  
Anna Lastuvkova ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Activation ◽  
Embryonic Stem ◽  
Regulatory Elements ◽  
Gene Promoters ◽  
Control Of Gene Expression ◽  
Precise Control ◽  
3D Genome ◽  
Gene Regulatory Elements ◽  
Gene Regulatory

Precise control of gene expression underpins normal development. This relies on mechanisms that enable communication between gene promoters and other regulatory elements. In embryonic stem cells (ESCs), the CDK-Mediator (CDK-MED) complex has been reported to physically link gene regulatory elements to enable gene expression and also prime genes for induction during differentiation. Here we discover that CDK-MED contributes little to 3D genome organisation in ESCs, but has a specific and essential role in controlling interactions between inactive gene regulatory elements bound by Polycomb repressive complexes (PRCs). These interactions are established by the canonical PRC1 (cPRC1) complex but rely on CDK-MED, which facilitates binding of cPRC1 to its target sites. Importantly, through separation of function experiments, we reveal that this collaboration between CDK-MED and cPRC1 in creating long-range interactions does not function to prime genes for induction during differentiation. Instead, we discover that priming relies on an interaction-independent mechanism whereby the CDK module supports core Mediator engagement with gene promoters to enable gene activation.

scholarly journals The global and promoter-centric 3D genome organization temporally resolved during a circadian cycle

2020 ◽  
Author(s):  
Masami Ando-Kuri ◽  
Rodrigo G. Arzate-Mejía ◽  
Jorg Morf ◽  
Jonathan Cairns ◽  
Cesar A. Poot-Hernández ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mouse Liver ◽  
Regulatory Elements ◽  
Open Chromatin ◽  
Chromatin Conformation ◽  
Gene Promoters ◽  
Circadian Gene ◽  
Circadian Genes ◽  
Physiological Importance ◽  
3D Genome

SummaryCircadian gene expression is essential for organisms to adjust cellular responses and anticipate daily changes in the environment. In addition to its physiological importance, the clock circuit represents an ideal, temporally resolved, system to study transcription regulation. Here, we analysed changes in spatial mouse liver chromatin conformation using genome-wide and promoter-capture Hi-C alongside daily oscillations in gene transcription in mouse liver. We found circadian topologically associated domains switched assignments to the transcriptionally active, open chromatin compartment and the inactive compartment at different hours of the day while their boundaries stably maintain their structure over time. Individual circadian gene promoters displayed maximal chromatin contacts at times of peak transcriptional output and the expression of circadian genes and contacted transcribed regulatory elements, or other circadian genes, was phase-coherent. Anchor sites of promoter chromatin loops were enriched in binding sites for liver nuclear receptors and transcription factors, some exclusively present in either rhythmic or stable contacts. The circadian 3D chromatin maps provided here identify the scales of chromatin conformation that parallel oscillatory gene expression and protein factors specifically associated with circadian or stable chromatin configurations.

scholarly journals Cell type-specific enhancer-promoter connectivity maps in the human brain and disease risk association

2019 ◽  
Author(s):  
Alexi Nott ◽  
Inge R. Holtman ◽  
Nicole G. Coufal ◽  
Johannes C.M. Schlachetzki ◽  
Miao Yu ◽  
...  
Keyword(s):  
Human Brain ◽  
Psychiatric Disorders ◽  
Complex Traits ◽  
Disease Risk ◽  
Cell Types ◽  
Regulatory Elements ◽  
Gene Promoters ◽  
Cell Type ◽  
Risk Variants ◽  
Cell Type Specific

AbstractUnique cell type-specific patterns of activated enhancers can be leveraged to interpret non-coding genetic variation associated with complex traits and diseases such as neurological and psychiatric disorders. Here, we have defined active promoters and enhancers for major cell types of the human brain. Whereas psychiatric disorders were primarily associated with regulatory regions in neurons, idiopathic Alzheimer’s disease (AD) variants were largely confined to microglia enhancers. Interactome maps connecting GWAS variants in cell type-specific enhancers to gene promoters revealed an extended microglia gene network in AD. Deletion of a microglia-specific enhancer harboring AD-risk variants ablated BIN1 expression in microglia but not in neurons or astrocytes. These findings revise and expand the genes likely to be influenced by non-coding variants in AD and suggest the probable brain cell types in which they function.One Sentence SummaryIdentification of cell type-specific regulatory elements in the human brain enables interpretation of non-coding GWAS risk variants.

scholarly journals Spatial genome re-organization between fetal and adult hematopoietic stem cells

2019 ◽  
Author(s):  
C Chen ◽  
W Yu ◽  
J Tober ◽  
P Gao ◽  
B He ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Target Genes ◽  
Three Dimensional ◽  
Gene Promoters ◽  
Loss Of Function ◽  
Dynamic Interactions ◽  
Hematopoietic Stem ◽  
3D Genome ◽  
Chromatin Interactions

AbstractFetal hematopoietic stem cells (HSCs) undergo a developmental switch to become adult HSCs. The functional properties of the HSCs change dramatically during this switch, including their cycling behavior, hematopoietic lineage outputs and proliferation rate. The relationship between three-dimensional (3D) genome organization, epigenomic state, and transcriptome is poorly understood during this critical developmental transition. Here we conducted a comprehensive survey of the 3D genome, epigenome and transcriptome of fetal and adult HSCs in mouse. We found that chromosomal compartments and topologically associating domains (TAD) are largely conserved between fetal and adult HSCs. However, there is a global trend of increased compartmentalization and TAD boundary strength in adult HSCs. In contrast, dynamics of intra-TAD chromatin interactions is much higher and more widespread, involving over a thousand gene promoters and distal enhancers. Such dynamic interactions target genes involved in cell cycle, metabolism, and hematopoiesis. These developmental-stage-specific enhancer-promoter interactions appear to be mediated by different sets of transcription factors in fetal and adult HSCs, such as TCF3 and MAFB in fetal HSCs, versus NR4A1 and GATA3 in adult HSCs. Loss-of-function studies of TCF3 confirms the role of TCF3 in mediating condition-specific enhancer-promoter interactions and gene regulation in fetal HSCs. In summary, our data suggest that the fetal-to-adult transition is accompanied by extensive changes in intra-TAD chromatin interactions that target genes underlying the phenotypic differences between fetal and adult HSCs.

In vivo evidence of interaction between interferon-stimulated gene factors and the interferon-stimulated response element

1989 ◽  
Vol 9 (8) ◽  
pp. 3533-3537
Author(s):  
R Pine ◽  
J E Darnell
Keyword(s):  
Gene Transcription ◽  
Gene Promoters ◽  
Cell Type ◽  
Response Element ◽  
Hypersensitive Sites

Constitutive and interferon-inducible DNase hypersensitive sites in vivo are located in interferon-stimulated gene promoters near sequences that specifically bind constitutive or interferon-inducible proteins in vitro. Induced sites and proteins are transient or maintained, depending on cell type. Interferon-stimulated gene transcription is transient or maintained in parallel.

scholarly journals In vivo evidence of interaction between interferon-stimulated gene factors and the interferon-stimulated response element.

1989 ◽  
Vol 9 (8) ◽  
pp. 3533-3537 ◽  
Author(s):  
R Pine ◽  
J E Darnell
Keyword(s):  
Gene Transcription ◽  
Gene Promoters ◽  
Cell Type ◽  
Response Element ◽  
Hypersensitive Sites

Constitutive and interferon-inducible DNase hypersensitive sites in vivo are located in interferon-stimulated gene promoters near sequences that specifically bind constitutive or interferon-inducible proteins in vitro. Induced sites and proteins are transient or maintained, depending on cell type. Interferon-stimulated gene transcription is transient or maintained in parallel.

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