Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genome graphs detect human polymorphisms in active epigenomic state during influenza infection [ATAC-seq]

ABSTRACT: Genetic variants, including mobile element insertions (MEIs), are known to impact the epigenome. We hypothesized that the use of a genome graph, which encapsulates genetic diversity, could reveal missing epigenomic signal. We tested this in a dataset obtained by sequencing the epigenome of monocyte-derived macrophages from 35 ancestrally diverse individuals before and after Influenza virus infection, which also allowed us to investigate the potential role of MEIs in immunity. After characterizing genetic variants in this cohort using linked-reads, including 5140 Alu, 316 L1, 94 SVAs and 48 ERVs, we incorporated them into a genome graph. Mapping epigenetic data to this graph revealed 2.5%, 3.0% and 2.3% novel peaks for H3K4me1 and H3K27ac ChIP-seq and ATAC-seq respectively. Notably, using a genome graph also modified quantitative trait loci estimates and we observed 375 polymorphic MEIs in active epigenomic state. For example, we found an AluYh3 polymorphism whose chromatin state changed after infection and that was associated with the expression of TRIM25, a gene that restricts influenza RNA synthesis. Our results demonstrate that graph genomes can reveal regulatory regions that would have been overlooked by other approaches.

ORGANISM(S): Homo sapiens

PROVIDER: GSE225704 | GEO | 2023/02/21

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Genome graphs detect human polymorphisms in active epigenomic state during influenza infection [ChIP-seq]

Project description:Genetic variants, including mobile element insertions (MEIs), are known to impact the epigenome. We hypothesized that the use of a genome graph, which encapsulates genetic diversity, could reveal missing epigenomic signal. We tested this in a dataset obtained by sequencing the epigenome of monocyte-derived macrophages from 35 ancestrally diverse individuals before and after Influenza virus infection, which also allowed us to investigate the potential role of MEIs in immunity. After characterizing genetic variants in this cohort using linked-reads, including 5140 Alu, 316 L1, 94 SVAs and 48 ERVs, we incorporated them into a genome graph. Mapping epigenetic data to this graph revealed 2.5%, 3.0% and 2.3% novel peaks for H3K4me1 and H3K27ac ChIP-seq and ATAC-seq respectively. Notably, using a genome graph also modified quantitative trait loci estimates and we observed 375 polymorphic MEIs in active epigenomic state. For example, we found an AluYh3 polymorphism whose chromatin state changed after infection and that was associated with the expression of TRIM25, a gene that restricts influenza RNA synthesis. Our results demonstrate that graph genomes can reveal regulatory regions that would have been overlooked by other approaches.

2023-02-21 | GSE225706 | GEO

Empirical Bayes Conditional Independence Graphs for Dense Regulatory Network Recovery

Project description:Motivation: Computational inference methods that make use of graphical models to extract regulatory networks from gene expression data can have difficulty reconstructing dense regions of a network, a consequence of both computational complexity and unreliable parameter estimation when sample size is small. As a result, identification of hub genes is of special difficulty for these methods.Methods: We present a new algorithm, Empirical Light Mutual Min (ELMM), for large network reconstruction that has properties well suited for dense graph recovery. ELMM reconstructs the undirected graph of a regulatory network using empirical Bayes conditional independence testing with a heuristic relaxation of independence constraints in dense areas of the graph. This relaxation allows only one gene of a pair with a putative relation to be aware of the network connection, an approach that is aimed at easing multiple testing problems associated with recovering densely connected structures.Results: Using in silico data, we show that ELMM has better performance than commonly used network inference algorithms including PC Algorithm, GeneNet, and ARACNE. We also apply ELMM to reconstruct a network among 5,400 genes expressed in human lung airway epithelium of healthy nonsmokers, healthy smokers, and smokers with pulmonary diseases assayed using microarrays. The analysis identifies dense subnetworks that are consistent with known regulatory relationships in the lung airway and also suggests novel hub regulatory relationships among a number of genes that play roles in oxidative stress, wound response, and secretion.

2024-06-05 | GSE32030 | GEO

Genetic deletion of ZNF91 in human embryonic stem cells leads to ectopic activation of SVAs and collective upregulation of KRAB zinc finger gene clusters

Project description:Transposable element (TE) invasions have shaped vertebrate genomes over the course of evolution. They have contributed an extra layer of species-specific gene regulation by providing novel transcription factor binding sites. In humans, SVA elements are one of three still active TE families, and approximately 2800 SVA insertions exist in the human genome, half of which are human-specific. TEs are often silenced by KRAB zinc finger (KZNF) proteins recruiting co-repressor proteins that establish a repressive chromatin state. A number of KZNFs have been reported to bind SVAs, but their individual contribution to repressing SVAs and their roles in suppressing SVA-mediated gene-regulatory effects remains elusive. We analyzed the genome-wide binding profile for ZNF91 in human cells and found that ZNF91 interacts with the VNTR region of SVAs. Through CRISPR-Cas9 mediated deletion of ZNF91 in human embryonic stem cells we established that loss of ZNF91 results in increased transcriptional activity of SVAs. In contrast, SVA activation was not observed upon genetic deletion of the ZNF611 gene encoding another strong SVA-interactor. Epigenetic profiling confirmed the loss of SVA repression in the absence of ZNF91 and revealed that mainly evolutionary young SVAs gain gene activation-associated epigenetic modifications. Genes close to activated SVAs showed a mild upregulation, indicating SVAs adopt properties of cis-regulatory elements in the absence of repression. Intriguingly, genome-wide de-repression of SVAs elicited the communal upregulation of KZNFs that reside in KZNF clusters. This phenomenon may provide new insights into the potential mechanisms utilized by the host genome to sense and counteract TE invasions.

2021-01-28 | GSE162571 | GEO

TALE transcription factors binding and transcriptional effect [ChIP-Seq]

Project description:Meis, Prep and Pbx1 TALE homeoproteins interactions with Hox proteins are essential for development and disease. Although Meis and Prep behave similarly in vitro, their in vivo activities remain largely unexplored. We show that Prep and Meis interact with largely independent sets of genomic sites and select different DNA binding sequences, with Prep associating mostly with promoters and house-keeping genes and Meis with promoter-remote regions and developmental genes. Hox target sequences associate strongly with Meis but not with Prep binding sites, while Pbx1 cooperates with both Prep and Meis. Accordingly, Meis1 shows strong genetic interaction with Pbx1 but not with Prep1. Meis1 and Prep1 nonetheless co-regulate a subset of genes, predominantly through opposing effects. Notably, the TALE homeoprotein binding profile subdivides Hox clusters into two domains differentially regulated by Meis1 and Prep1. After duplication of the ancestral gene, Meis and Prep thus specialized their interactions but maintained significant regulatory coordination.

2013-03-31 | GSE39608 | GEO

TALE transcription factors binding and transcriptional effect [RNA-Seq]

2013-03-31 | GSE39605 | GEO

TALE transcription factors binding and transcriptional effect [ChIP-Seq]

2013-03-31 | E-GEOD-39608 | biostudies-arrayexpress

Mini-heterochromatin domains constrain the cis-regulatory impact of SVA transposons in human brain development and disease

Project description:SVA retrotransposons remain active in humans and contribute to individual genetic variation. Polymorphic SVA alleles harbor gene-regulatory potential and can cause genetic disease. However, how SVA insertions are controlled and functionally impact human disease is unknown. Here, we dissect the epigenetic regulation and influence of SVAs in cellular models of X-linked dystonia-parkinsonism (XDP), a neurodegenerative disorder caused by an SVA insertion at the TAF1 locus. We demonstrate that the KRAB zinc finger protein ZNF91 establishes H3K9me3 and DNA methylation over SVAs, including polymorphic alleles, in human neural progenitor cells. The resulting mini-heterochromatin domains attenuate the cis-regulatory impact of SVAs. This is critical for XDP pathology; removal of local heterochromatin severely aggravates the XDP molecular phenotype, resulting in increased TAF1 intron retention and reduced expression. Our results provide unique mechanistic insights into how human polymorphic transposon insertions are recognized, and their regulatory impact constrained by an innate epigenetic defense system.

2023-11-01 | GSE245093 | GEO

A hidden layer of structural variation in transposable elements reveals potential genetic modifiers in human disease-risk loci

Project description:Genome-wide association studies (GWAS) have been highly informative in discovering disease-associated loci, but are not designed to capture all structural variations in the human genome. Using long-read sequencing data, we discovered widespread structural variation within SVA (Sine-VNTR-Alu) elements, a class of great-ape specific transposable elements with gene-regulatory roles, which represents a major source of structural variability in the human population. We highlight the presence of structurally variable SVAs (SV-SVAs) in neurological disease-associated loci, and further associate SV-SVAs to disease-associated SNPs and differential gene expression using luciferase assays and expression quantitative trait loci data. Finally, we genetically deleted SV-SVAs in the BIN1 and CD2AP Alzheimer-associated risk loci and in the BCKDK Parkinson disease-associated risk locus and assessed multiple aspects of their gene-regulatory influence in a human neuronal context. Together, this study reveals a novel layer of genetic variation in transposable elements that may contribute to identification of the structural variants that are the actual drivers of disease-associations of GWAS loci.

2022-01-17 | GSE167409 | GEO

TALE transcription factors binding and transcriptional effect [RNA-Seq]

2013-03-31 | E-GEOD-39605 | biostudies-arrayexpress

Specific genomic features underlie the co-option of SVA transposons as cis-regulatory elements in the human genome

Project description:Domestication of transposable elements (TEs) into functional cis-regulatory elements is a widespread phenomenon. However, why some TEs are co-opted as functional enhancers while others are not is underappreciated. SINE-Vntr-Alus (SVAs) are the youngest group of transposons in the human genome, where ~3,700 copies are annotated, nearly half of which are human-exclusive. Many studies indicated that the SVAs are among the most frequently co-opted TEs in human gene regulation, but the mechanisms underlying such process have not yet been thoroughly investigated. Here, we leveraged CRISPR-interference (CRISPRi), computational and functional genomics to elucidate the genomic features that underlie SVA domestication into human stem-cell gene regulation. We found that ~750 SVAs are co-opted as functional cis-regulatory elements in human induced Pluripotent Stem Cells. Co-opted SVAs are significantly closer to genes and harbor more transcription factor binding sites than the not co-opted ones. We show that a long DNA-motif composed of flanking YY1/2 and OCT4 binding sites is enriched in the co-opted SVAs, and that these two factors bind, as predicted, near each other on the TE sequence. Repression of all the ~750 co-opted SVAs by CRISPRi in a line with stem-like properties (NCCIT) led to loss of YY1/OCT4 binding and alteration of neighboring gene expression. Ultimately, SVA repression resulted in ~3,000 differentially expressed genes, 131 of which were the nearest gene to an annotated SVA. In summary, we demonstrated that SVAs contribute significantly to human gene regulation, and that both genomic location and sequence composition contribute to SVA domestication in the gene regulatory networks.

2022-01-04 | GSE192951 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data