scholarly journals Comprehensive analysis of epigenetic signatures of mammalian transcription control

2021 ◽  
Author(s):  
Guillaume Devailly ◽  
Anagha Joshi
Keyword(s):  
Mammalian Cell ◽  
Comprehensive Analysis ◽  
Transcription Control ◽  
Sequencing Technologies ◽  
Transcription Profiles ◽  
Genome Wide ◽  
A Genome ◽  
Epigenetic Signatures ◽  
Transcriptional Landscape

Advances in sequencing technologies have enabled exploration of epigenetic and transcription profiles at a genome-wide level. Epigenetic and transcriptional landscape is now available across hundreds of mammalian cell and tissue...

scholarly journals Comprehensive analysis of epigenetic signatures of human transcription control†

2020 ◽  
Author(s):  
Guillaume Devailly ◽  
Anagha Joshi
Keyword(s):  
Transcription Termination ◽  
Epigenetic Modifications ◽  
Comprehensive Analysis ◽  
Transcription Control ◽  
Transcription Start Sites ◽  
Sequencing Technologies ◽  
Transcription Profiles ◽  
A Genome ◽  
Hypotheses Generation ◽  
Epigenetic Signatures

Advances in sequencing technologies have enabled exploration of epigenetic and transcription profiles at a genome-wide level. The epigenetic and transcriptional landscape is now available in hundreds of mammalian cell and tissue contexts. Many studies have performed multi-omics analyses using these datasets to enhance our understanding of relationships between epigenetic modifications and transcription regulation. Nevertheless, most studies so far have focused on the promoters/enhancers and transcription start sites, and other features of transcription control including exons, introns and transcription termination remain under explored. We investigated interplay between epigenetic modifications and diverse transcription features using the data generated by the Roadmap Epigenomics project. A comprehensive analysis of histone modifications, DNA methylation, and RNA-seq data of about thirty human cell lines and tissue types, allowed us to confirm the generality of previously described relations, as well as to generate new hypotheses about the interplay between epigenetic modifications and transcript features. Importantly, our analysis included previously under-explored features of transcription control namely, transcription termination sites, exon-intron boundaries, middle exons and exon inclusion ratio. We have made the analyses freely available to the scientific community at joshiapps.cbu.uib.no/perepigenomics_app/ for easy exploration, validation and hypotheses generation.

scholarly journals DNA methylation marks inter-nucleosome linker regions throughout the human genome

2013 ◽  
Author(s):  
Benjamin P. Berman ◽  
Yaping Liu ◽  
Theresa K. Kelly
Keyword(s):  
Dna Methylation ◽  
Human Genome ◽  
Ctcf Binding ◽  
Gene Promoters ◽  
Cpg Dinucleotides ◽  
Sequencing Technologies ◽  
Nucleosome Organization ◽  
Genome Wide ◽  
A Genome ◽  
Sequencing Studies

Background: Nucleosome organization and DNA methylation are two mechanisms that are important for proper control of mammalian transcription, as well as epigenetic dysregulation associated with cancer. Whole-genome DNA methylation sequencing studies have found that methylation levels in the human genome show periodicities of approximately 190 bp, suggesting a genome-wide relationship between the two marks. A recent report (Chodavarapu et al., 2010) attributed this to higher methylation levels of DNA within nucleosomes. Here, we analyzed a number of published datasets and found a more compelling alternative explanation, namely that methylation levels are highest in linker regions between nucleosomes. Results: Reanalyzing the data from (Chodavarapu et al., 2010), we found that nucleosome-associated methylation could be strongly confounded by known sequence-related biases of the next-generation sequencing technologies. By accounting for these biases and using an unrelated nucleosome profiling technology, NOMe-seq, we found that genome-wide methylation was actually highest within linker regions occurring between nucleosomes in multi-nucleosome arrays. This effect was consistent among several methylation datasets generated independently using two unrelated methylation assays. Linker-associated methylation was most prominent within long Partially Methylated Domains (PMDs) and the positioned nucleosomes that flank CTCF binding sites. CTCF adjacent nucleosomes retained the correct positioning in regions completely devoid of CpG dinucleotides, suggesting that DNA methylation is not required for proper nucleosomes positioning. Conclusions: The biological mechanisms responsible for DNA methylation patterns outside of gene promoters remain poorly understood. We identified a significant genome-wide relationship between nucleosome organization and DNA methylation, which can be used to more accurately analyze and understand the epigenetic changes that accompany cancer and other diseases.

scholarly journals Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation

2016 ◽  
Vol 2 (6) ◽  
pp. e1501678 ◽  
Author(s):  
Till F. M. Andlauer ◽  
Dorothea Buck ◽  
Gisela Antony ◽  
Antonios Bayas ◽  
Lukas Bechmann ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Genome Wide Association Study ◽  
Immune Cell ◽  
Susceptibility Loci ◽  
Genome Wide ◽  
A Genome ◽  
Genetic Substructure ◽  
Epigenetic Signatures ◽  
Folate Cycle ◽  
Ms Pathogenesis

We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genesL3MBTL3,MAZ,ERG, andSHMT1. The lead variant atSHMT1was replicated in an independent Sardinian cohort. Products of the genesL3MBTL3,MAZ, andERGplay important roles in immune cell regulation.SHMT1encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis.

scholarly journals The first decade of estrogen receptor cistromics in breast cancer

2016 ◽  
Vol 229 (2) ◽  
pp. R43-R56 ◽  
Author(s):  
Koen D Flach ◽  
Wilbert Zwart
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Transcription Factor ◽  
Tiling Array ◽  
Estrogen Receptor Α ◽  
Sequencing Technologies ◽  
Hormone Receptor Positive ◽  
Genome Wide ◽  
A Genome ◽  
On Chip

The advent of genome-wide transcription factor profiling has revolutionized the field of breast cancer research. Estrogen receptor α (ERα), the major drug target in hormone receptor-positive breast cancer, has been known as a key transcriptional regulator in tumor progression for over 30 years. Even though this function of ERα is heavily exploited and widely accepted as an Achilles heel for hormonal breast cancer, only since the last decade we have been able to understand how this transcription factor is functioning on a genome-wide scale. Initial ChIP-on-chip (chromatin immunoprecipitation coupled with tiling array) analyses have taught us that ERα is an enhancer-associated factor binding to many thousands of sites throughout the human genome and revealed the identity of a number of directly interacting transcription factors that are essential for ERα action. More recently, with the development of massive parallel sequencing technologies and refinements thereof in sample processing, a genome-wide interrogation of ERα has become feasible and affordable with unprecedented data quality and richness. These studies have revealed numerous additional biological insights into ERα behavior in cell lines and especially in clinical specimens. Therefore, what have we actually learned during this first decade of cistromics in breast cancer and where may future developments in the field take us?

scholarly journals DNA methylation marks inter-nucleosome linker regions throughout the human genome

2013 ◽  
Author(s):  
Benjamin P. Berman ◽  
Yaping Liu ◽  
Theresa K. Kelly
Keyword(s):  
Dna Methylation ◽  
Human Genome ◽  
Ctcf Binding ◽  
Gene Promoters ◽  
Cpg Dinucleotides ◽  
Sequencing Technologies ◽  
Nucleosome Organization ◽  
Genome Wide ◽  
A Genome ◽  
Sequencing Studies

Background: Nucleosome organization and DNA methylation are two mechanisms that are important for proper control of mammalian transcription, as well as epigenetic dysregulation associated with cancer. Whole-genome DNA methylation sequencing studies have found that methylation levels in the human genome show periodicities of approximately 190 bp, suggesting a genome-wide relationship between the two marks. A recent report (Chodavarapu et al., 2010) attributed this to higher methylation levels of DNA within nucleosomes. Here, we analyzed a number of published datasets and found a more compelling alternative explanation, namely that methylation levels are highest in linker regions between nucleosomes. Results: Reanalyzing the data from (Chodavarapu et al., 2010), we found that nucleosome-associated methylation could be strongly confounded by known sequence-related biases of the next-generation sequencing technologies. By accounting for these biases and using an unrelated nucleosome profiling technology, NOMe-seq, we found that genome-wide methylation was actually highest within linker regions occurring between nucleosomes in multi-nucleosome arrays. This effect was consistent among several methylation datasets generated independently using two unrelated methylation assays. Linker-associated methylation was most prominent within long Partially Methylated Domains (PMDs) and the positioned nucleosomes that flank CTCF binding sites. CTCF adjacent nucleosomes retained the correct positioning in regions completely devoid of CpG dinucleotides, suggesting that DNA methylation is not required for proper nucleosomes positioning. Conclusions: The biological mechanisms responsible for DNA methylation patterns outside of gene promoters remain poorly understood. We identified a significant genome-wide relationship between nucleosome organization and DNA methylation, which can be used to more accurately analyze and understand the epigenetic changes that accompany cancer and other diseases.

scholarly journals Genome-wide dysregulation of histone acetylation in the Parkinson’s disease brain

2019 ◽  
Author(s):  
Lilah Toker ◽  
Gia T Tran ◽  
Janani Sundaresan ◽  
Ole-Bjørn Tysnes ◽  
Guido Alves ◽  
...  
Keyword(s):  
Histone Acetylation ◽  
Chromatin Immunoprecipitation ◽  
Genetic Risk ◽  
Neurodegenerative Disorder ◽  
Unknown Etiology ◽  
Transcriptomic Data ◽  
Genome Wide ◽  
A Genome ◽  
Chromatin Immunoprecipitation Sequencing ◽  
Epigenetic Signatures

AbstractParkinson disease (PD) is a complex neurodegenerative disorder of largely unknown etiology. While several genetic risk factors have been identified, the involvement of epigenetics in the pathophysiology of PD is mostly unaccounted for. We conducted a histone acetylome-wide association study in PD, using brain tissue from two independent cohorts of cases and controls. Immunoblotting revealed increased acetylation at several histone sites in PD, with the most prominent change observed for H3K27, a marker of active promoters and enhancers. Chromatin immunoprecipitation sequencing (ChIP-seq) further indicated that H3K27 hyperacetylation in the PD brain is a genome-wide phenomenon, with a strong predilection for genes implicated in the disease, including SNCA, PARK7, PRKN and MAPT. Integration of the ChIP-seq with transcriptomic data revealed that the correlation between promoter H3K27 acetylation and gene expression is attenuated in PD patients, suggesting that H3K27 acetylation may be decoupled from transcription in the PD brain. Our findings strongly suggest that dysregulation of histone acetylation plays an important role in the pathophysiology of PD and identify novel epigenetic signatures associated with the disease.

scholarly journals ChiRA: an integrated framework for chimeric read analysis from RNA-RNA interactome and RNA structurome data

GigaScience ◽  
2021 ◽  
Vol 10 (2) ◽  
Author(s):  
Pavankumar Videm ◽  
Anup Kumar ◽  
Oleg Zharkov ◽  
Björn Andreas Grüning ◽  
Rolf Backofen
Keyword(s):  
Rna Structure ◽  
Complete Analysis ◽  
Published Data ◽  
Random Choice ◽  
Sequencing Technologies ◽  
Genome Wide ◽  
A Genome ◽  
Interaction Partners ◽  
Rna Interaction ◽  
New Interactions

Abstract Background With the advances in next-generation sequencing technologies, it is possible to determine RNA-RNA interaction and RNA structure predictions on a genome-wide level. The reads from these experiments usually are chimeric, with each arm generated from one of the interaction partners. Owing to short read lengths, often these sequenced arms ambiguously map to multiple locations. Thus, inferring the origin of these can be quite complicated. Here we present ChiRA, a generic framework for sensitive annotation of these chimeric reads, which in turn can be used to predict the sequenced hybrids. Results Grouping reference loci on the basis of aligned common reads and quantification improved the handling of the multi-mapped reads in contrast to common strategies such as the selection of the longest hit or a random choice among all hits. On benchmark data ChiRA improved the number of correct alignments to the reference up to 3-fold. It is shown that the genes that belong to the common read loci share the same protein families or similar pathways. In published data, ChiRA could detect 3 times more new interactions compared to existing approaches. In addition, ChiRAViz can be used to visualize and filter large chimeric datasets intuitively. Conclusion ChiRA tool suite provides a complete analysis and visualization framework along with ready-to-use Galaxy workflows and tutorials for RNA-RNA interactome and structurome datasets. Common read loci built by ChiRA can rescue multi-mapped reads on paralogous genes without requiring any information on gene relations. We showed that ChiRA is sensitive in detecting new RNA-RNA interactions from published RNA-RNA interactome datasets.

scholarly journals Targeted control of toxin production by a mobile genetic element in Streptococcus pneumoniae

2020 ◽  
Author(s):  
Emily Stevens ◽  
Daniel J. Morse ◽  
Dora Bonini ◽  
Seána Duggan ◽  
Tarcisio Brignoli ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Nuclease Activity ◽  
Toxin Production ◽  
Helicase Domain ◽  
Human Pathogen ◽  
Genome Wide ◽  
A Genome ◽  
Invasive Diseases ◽  
Transcriptional Landscape ◽  
Integrative And Conjugative Element

Introductory ParagraphStreptococcus pneumoniae is a major human pathogen that can cause severe invasive diseases such as pneumonia, septicaemia and meningitis1–3. Young children are at a particularly high risk, with an estimated 800,000 deaths worldwide in those under five attributable to invasive pneumococcal disease each year1–3. The cytolytic toxin pneumolysin (Ply) is a primary virulence factor for this bacterium, however, despite its importance to both the colonisation and pathogenic capabilities of this pathogen, the regulation of its expression is not well defined4–7. Using a genome-wide association approach we identified over a hundred potential affectors of Ply activity, including the Integrative and Conjugative Element (ICE) ICESp23FST818. This regulatory effect is mediated through the activity of a novel modular protein, ZomB, which has an N-terminal UvrD-like helicase domain followed by two Cas4-like nuclease domains. The ZomB protein has potent ATP-dependent nuclease activity and binds specifically to the DNA containing a BOX repeat region that forms part of the ply operon. We hypothesise that with over 100 BOX regions across the pneumococcal genome, the acquisition of the zomB gene on ICESp23FST81 has the potential to re-wire the transcriptional landscape of this major human pathogen.

scholarly journals Dense and accurate whole-chromosome haplotyping of individual genomes

2017 ◽  
Author(s):  
David Porubsky ◽  
Shilpa Garg ◽  
Ashley D. Sanders ◽  
Jan O. Korbel ◽  
Victor Guryev ◽  
...  
Keyword(s):  
Target Genes ◽  
Chromosome Length ◽  
Single Individual ◽  
Sequencing Data ◽  
Individual Genome ◽  
Sequencing Technologies ◽  
Biological Phenomena ◽  
Genome Wide ◽  
A Genome ◽  
Long Read

ABSTRACTThe diploid nature of the genome is neglected in many analyses done today, where a genome is perceived as a set of unphased variants with respect to a reference genome. Many important biological phenomena such as compound heterozygosity and epistatic effects between enhancers and target genes, however, can only be studied when haplotype-resolved genomes are available. This lack of haplotype-level analyses can be explained by a dearth of methods to produce dense and accurate chromosome-length haplotypes at reasonable costs. Here we introduce an integrative phasing strategy that combines global, but sparse haplotypes obtained from strand-specific single cell sequencing (Strand-seq) with dense, yet local, haplotype information available through long-read or linked-read sequencing. Our experiments provide comprehensive guidance on favorable combinations of Strand-seq libraries and sequencing coverages to obtain complete and genome-wide haplotypes of a single individual genome (NA12878) at manageable costs. We were able to reliably assign > 95% of alleles to their parental haplotypes using as few as 10 Strand-seq libraries in combination with 10-fold coverage PacBio data or, alternatively, 10X Genomics linked-read sequencing data. We conclude that the combination of Strand-seq with different sequencing technologies represents an attractive solution to chart the unique genetic variation of diploid genomes.

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