Evolution of Replication Origins in Vertebrate Genomes: Rapid Turnover Despite Selective Constraints [SNS-seq]
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ABSTRACT:
PROVIDER: PRJNA489388 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7788732_1.fastq.gz | Fastqsanger.gz | |||
| SRR7788732_2.fastq.gz | Fastqsanger.gz | |||
| SRR7788733_1.fastq.gz | Fastqsanger.gz | |||
| SRR7788733_2.fastq.gz | Fastqsanger.gz | |||
| SRR7788734_1.fastq.gz | Fastqsanger.gz |
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Project description:Background: The replication program of vertebrate genomes is driven by the chromosomal distribution and timing of activation of ten of thousands replication origins. Genome-wide studies have shown the frequent association of origins with promoters and CpG islands, and their enrichment in G-quadruplexes sequence motifs (G4). However the genetic determinants driving their activity remain poorly understood. To gain insight on functional constraints operating on replication origins and on their spatial distribution, we conduct the first evolutionary comparison of genome-wide origins maps across vertebrates. Results: We generated a high resolution genome-wide map of chicken replication origins (the first of a bird genome), and performed an extensive comparison with human and mouse maps. The analysis of intra-species polymorphism revealed a strong depletion of genetic diversity on a ∼ 40bp region centered on the replication initiation loci. Surprisingly, this depletion in genetic diversity is not linked to the presence of G4 motifs, nor to the association with promoters or CpG islands. In contrast, we also show that origins have experienced a rapid turnover during vertebrates evolution, since pairwise comparisons of origin maps revealed that only 4 to 24% of them are conserved between any two species. Conclusions: This study unravels the existence of a novel genetic determinant of replication origins, whose precise functional role remains to be determined. Despite the importance of replication initiation activity for the fitness of organisms, the distribution of replication origins along vertebrate chromosomes is highly flexible.
2019-03-06 | GSE119488 | GEO
Project description:The replication program of vertebrate genomes is driven by the chromosomal distribution and timing of activation of tens of thousands of replication origins. Genome-wide studies have shown the association of origins with promoters and CpG islands, and their enrichment in G-quadruplex motifs (G4). However, the genetic determinants driving their activity remain poorly understood. To gain insight on the constraints operating on origins, we conducted the first evolutionary comparison of origins across vertebrates. We generated a genome-wide map of chicken origins (the first of a bird genome), and performed a comparison with human and mouse maps. The analysis of intra-species polymorphism revealed a strong depletion of genetic diversity at the core of replication initiation loci. This depletion is not linked to the presence of G4 motifs, promoters or CpG islands. In contrast, we show that origins experienced a rapid turnover during vertebrate evolution, since pairwise comparisons of origin maps revealed that <24% of them are conserved among vertebrates. This study unravels the existence of a novel determinant of origins, the precise functional role of which remains to be determined. Despite the importance of replication initiation for the fitness of organisms, the distribution of origins along vertebrate chromosomes is highly flexible.
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Project description:Genome-wide comparisons of transcription factor binding sites in different species allow for a direct evaluation of the evolutionary constraints that shape transcription factor binding landscapes. To gain insights into the evolution of the PPARg-dependent transcriptional network we obtained binding data for PPARg, RXR and PU.1 in human macrophages and compared the profiles to matching data from mouse macrophages. We found that PPARg binding was highly divergent and only 5% of the PPARg bound regions were occupied in both species. Despite the low conservation of PPARg binding sites, conserved PPARg target genes contribute more than 30% to the functional target genes identified in human macrophages. In addition conserved target genes are strongly enriched for lipid metabolic functions. We detected the lineage-specification factor PU.1 at the majority of human PPARg binding sites. This confirmed the juxtaposed binding configuration found in mouse macrophages and demonstrated the preservation of tissue-specific adjacent PPARg-Pu.1 binding in the absence of individual binding site conservation. Finally, based on this of PPARg and PU.1 binding between human and mouse we suggest a mechanism by which PU.1 facilitates PPARg binding site turnover in macrophages. Comparison of RNAs level in Rosiglitazone (RSG) and vehicle (DMSO) treated PMA differentiated THP-1 cells over a timecourse from 0.5h to 12h
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Project description:Genome-wide comparisons of transcription factor binding sites in different species allow for a direct evaluation of the evolutionary constraints that shape transcription factor binding landscapes. To gain insights into the evolution of the PPARg-dependent transcriptional network, we obtained binding data for PPARg, RXR and PU.1 in human macrophages and compared the profiles to matching data from mouse macrophages (Lefterova et al. 2010 (PMID 20176806); GSE21314). We found that PPARg binding was highly divergent and only 5% of the PPARg-bound regions were occupied in both species. Despite the low conservation of PPARg binding sites, conserved PPARg target genes contribute more than 30% to the functional target genes identified in human macrophages. In addition, conserved target genes are strongly enriched for lipid metabolic functions. We detected the lineage-specification factor PU.1 at the majority of human PPARg binding sites. This confirmed the juxtaposed binding configuration found in mouse macrophages and demonstrated the preservation of tissue-specific adjacent PPARg-Pu.1 binding in the absence of individual binding site conservation. Finally, based on this PPARg and PU.1 binding between human and mouse, we suggest a mechanism by which PU.1 facilitates PPARg binding site turnover in macrophages. Genome-wide location analysis for 3 transcription factors (PPARg, RXR and PU.1) in a human monocytic cell line (THP-1). This submission represents the human binding data component of the study.
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2015-06-23 | E-GEOD-69807 | biostudies-arrayexpress
Project description:At every cell cycle, faithful inheritance of metazoan genomes requires the concerted activation of thousands of DNA replication origins. However, which genetic and chromatin features define metazoan replication start sites remains largely unknown. Here, we delineate the origin repertoire of the Drosophila genome at high resolution. We address the role of origin-proximal G-quadruplexes and show their ability to transiently stall replication forks in vivo. We dissect the chromatin configuration of replication origins and identify a rich spatial organization of chromatin features at initiation sites. DNA shape and chromatin configurations, not strict sequence specificity, mark and predict replication origins in higher eukaryotes. We further examine the link between transcription and origin firing and reveal that modulation of origin activity across cell types is intimately linked to cell-type-specific transcriptional programs. Our study unravels conserved origin features and provides unique insights into the relationship between DNA topology, chromatin, transcription and replication initiation across metazoa. Our dataset consists of SNS-Seq profiles in Drosophila S2 and Bg3 cells. Small nascent leading strands (SNS) have been purified with an enhanced sensitivity SNS purification protocol. For standard SNS-Seq experiments (from pooled gradient fractions, denoted as "pool"), SNS were purified from two biological replicates. For single-fraction SNS-Seq experiments, two libraries were prepared for each fraction. The genomic coordinates of S2 and Bg3 replication origins are also provided.
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Project description:Thousands of large intervening non-coding RNAs (lincRNAs) have been identified in mammals. To better understand the evolution and functions of these enigmatic RNAs, we used chromatin marks, poly(A)-site mapping and RNA-Seq data, to identify more than 550 distinct lincRNAs in zebrafish. Although these shared many characteristics with mammalian lincRNAs, only 29 had detectable sequence similarity with putative mammalian orthologs, typically restricted to a single short region of high conservation. Other lincRNAs had conserved genomic locations without detectable sequence conservation. Antisense reagents targeting conserved regions of two zebrafish lincRNAs caused developmental defects. Reagents targeting splice sites caused the same defects and were rescued by adding either the mature lincRNA or its human or mouse ortholog. Our study provides a roadmap for identification and analysis of lincRNAs in model organisms and shows that lincRNAs play crucial biological roles during embryonic development with functionality conserved despite limited sequence conservation. H3K4me3, H3K36me3 chromatin maps, 3P-Seq and RNA-Seq were used to identify lincRNAs in the zebrafish genome
2011-12-22 | E-GEOD-32880 | biostudies-arrayexpress
Project description:Genome-wide comparisons of transcription factor binding sites in different species allow for a direct evaluation of the evolutionary constraints that shape transcription factor binding landscapes. To gain insights into the evolution of the PPARg-dependent transcriptional network we obtained binding data for PPARg, RXR and PU.1 in human macrophages and compared the profiles to matching data from mouse macrophages. We found that PPARg binding was highly divergent and only 5% of the PPARg bound regions were occupied in both species. Despite the low conservation of PPARg binding sites, conserved PPARg target genes contribute more than 30% to the functional target genes identified in human macrophages. In addition conserved target genes are strongly enriched for lipid metabolic functions. We detected the lineage-specification factor PU.1 at the majority of human PPARg binding sites. This confirmed the juxtaposed binding configuration found in mouse macrophages and demonstrated the preservation of tissue-specific adjacent PPARg-Pu.1 binding in the absence of individual binding site conservation. Finally, based on this of PPARg and PU.1 binding between human and mouse we suggest a mechanism by which PU.1 facilitates PPARg binding site turnover in macrophages.
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