Active DNA demethylation at enhancers during the vertebrate phylotypic period
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA281741 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1983670.fastq.gz | Fastqsanger.gz | |||
| SRR1983680.fastq.gz | Fastqsanger.gz | |||
| SRR1983690.fastq.gz | Fastqsanger.gz | |||
| SRR1983700.fastq.gz | Fastqsanger.gz | |||
| SRR1983710.fastq.gz | Fastqsanger.gz |
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Project description:The vertebrate body plan and organs are shaped during a highly conserved embryonic phase called the phylotypic stage, however the mechanisms that guide the epigenome through this transition and their evolutionary conservation remain elusive. Here we report widespread DNA demethylation of thousands of enhancers during the phylotypic period in zebrafish, Xenopus and mouse. These dynamic enhancers are linked to essential developmental genes that display coordinated transcriptional and epigenomic changes in the diverse vertebrates during embryogenesis. Phylotypic stage-specific binding of Tet proteins to (hydroxy)methylated DNA, and enrichment of hydroxymethylcytosine on these enhancers, implicated active DNA demethylation in this process. Furthermore, loss of function of Tet1/2/3 in zebrafish caused reduced chromatin accessibility and increased methylation levels specifically on these enhancers, indicative of DNA methylation being an upstream regulator of phylotypic enhancer function. Overall, our study reveals a novel regulatory module associated with the most conserved phase of vertebrate embryogenesis and uncovers an ancient developmental role for the Tet dioxygenases.
2016-01-27 | PXD001164 | Pride
Project description:The vertebrate body plan and organs are shaped during a conserved embryonic phase called the phylotypic stage, however the mechanisms that guide the epigenome through this transition and their evolutionary conservation remain elusive. Here we report widespread DNA demethylation of enhancers during the phylotypic period in zebrafish, Xenopus and mouse. These enhancers are linked to developmental genes that display coordinated transcriptional and epigenomic changes in the diverse vertebrates during embryogenesis. Binding of Tet proteins to (hydroxy)methylated DNA, and enrichment of hydroxymethylcytosine on these regions, implicated active DNA demethylation in this process. Furthermore, loss of function of Tet1/2/3 in zebrafish caused reduced chromatin accessibility and increased methylation levels specifically on these enhancers, indicative of DNA methylation being an upstream regulator of phylotypic enhancer function. Overall, our study reveals a novel regulatory module associated with the most conserved phase of vertebrate embryogenesis and uncovers an ancient developmental role for the Tet dioxygenases.
2016-01-29 | GSE68087 | GEO
Project description:The vertebrate body plan and organs are shaped during a conserved embryonic phase called the phylotypic stage. However, the mechanisms that guide the epigenome through this transition and their evolutionary conservation remain elusive. Here we report widespread DNA demethylation of enhancers during the phylotypic period in zebrafish, Xenopus tropicalis and mouse. These enhancers are linked to developmental genes that display coordinated transcriptional and epigenomic changes in the diverse vertebrates during embryogenesis. Binding of Tet proteins to (hydroxy)methylated DNA and enrichment of 5-hydroxymethylcytosine in these regions implicated active DNA demethylation in this process. Furthermore, loss of function of Tet1, Tet2 and Tet3 in zebrafish reduced chromatin accessibility and increased methylation levels specifically at these enhancers, indicative of DNA methylation being an upstream regulator of phylotypic enhancer function. Overall, our study highlights a regulatory module associated with the most conserved phase of vertebrate embryogenesis and suggests an ancient developmental role for Tet dioxygenases.
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Project description:One of the central issues in evolutionary developmental biology is how we can formulate the relationships between evolutionary and developmental processes. Two major models have been proposed: the 'funnel-like' model, in which the earliest embryo shows the most conserved morphological pattern, followed by diversifying later stages, and the 'hourglass' model, in which constraints are imposed to conserve organogenesis stages, which is called the phylotypic period. Here we perform a quantitative comparative transcriptome analysis of several model vertebrate embryos and show that the pharyngula stage is most conserved, whereas earlier and later stages are rather divergent. These results allow us to predict approximate developmental timetables between different species, and indicate that pharyngula embryos have the most conserved gene expression profiles, which may be the source of the basic body plan of vertebrates. This SuperSeries is composed of the SubSeries listed below.
2011-04-05 | GSE28391 | GEO
Project description:One of the central issues in evolutionary developmental biology is how we can formulate the relationships between evolutionary and developmental processes. Two major models have been proposed: the 'funnel-like' model, in which the earliest embryo shows the most conserved morphological pattern, followed by diversifying later stages, and the 'hourglass' model, in which constraints are imposed to conserve organogenesis stages, which is called the phylotypic period. Here we perform a quantitative comparative transcriptome analysis of several model vertebrate embryos and show that the pharyngula stage is most conserved, whereas earlier and later stages are rather divergent. These results allow us to predict approximate developmental timetables between different species, and indicate that pharyngula embryos have the most conserved gene expression profiles, which may be the source of the basic body plan of vertebrates. Refer to individual Series. This SuperSeries is composed of the following subset Series: GSE28388: [E-MTAB-366] Transcription profiling by array of chicken embryos at 15 different stages GSE28389: [E-MTAB-368] Transcription profiling by array of mouse embryos at 8 different stages GSE28390: [E-MTAB-369] Transcription profiling by array of Xenopus laevis embryos at 15 different stages Refer to individual Series
2011-04-05 | E-GEOD-28391 | biostudies-arrayexpress
Project description:The DNA methylation program is at the bottom layer of the epigenetic regulatory cascade of vertebrate development. While the methylation at C-5 position of the cytosine (C) residues on the vertebrate genomes is achieved through the catalytic activities of the DNA methyltransferases (DNMTs), the conversion of the methylated cytosine (5mC) could be accomplished by the combined actions of the TET enzyme and DNA repair. Interestingly, it has been found recently that the mouse and human DNMTs also possess active DNA demethylation activity in vitro in a Ca2+- and redox condition-dependent manner. We report here the study of tracking down the fate of the methyl group removed from 5mC on DNA during in vitro demethylation reaction by mouse de novo DNMTs, i.e. DNMT3A and DNMT3B. Remarkably, the methyl group becomes covalently linked to the catalytic cysteines utilized by the two de novo DNMTs in their DNA methylation reactions. Thus, the forward and reverse reactions of DNA methylations by the DNMTs may utilize the same cysteine residue(s) as the active site despite of their distinctive pathways. Secondly, we demonstrate that active DNA demethylation of a heavily methylated GFP reporter plasmid by ectopically expressed DNMT3A or DNMT3B occurs in vivo in transfected human HEK 293 cells in culture. Furthermore, the extent of DNA demethylation by the DNMTs in this cell-based system is affected by Ca2+ homeostasis as well as by mutation of their putative active cysteines. These findings substantiate the roles of the vertebrate DNMTs as double-edged swords in DNA methylation-demethylation in vitro as well as in a cellular context.
2022-02-24 | PXD003401 | Pride
Project description:What genomic changes led to the origin of vertebrates remains a mystery. On the one hand, animal evolution is thought to be driven mostly by changes in the cis-regulatory regions of a shared conserved and toolkit of developmental genes. On the other hand, vertebrates experienced two rounds of whole genome duplication (WGD) that increased their gene repertoire, particularly of regulatory genes controlling embryo development. To shed light into the origin and evolution of the vertebrate regulatory genome, we have generated an unprecedented transcriptomic and epigenomic resource for the non-duplicated genome of the European amphioxus, a closely related invertebrate chordate. These data include RNA-seq for more than 35 developmental stages and adult tissues, CAGE-seq, ChIP-seq, bisulphite-seq and ATAC-seq for several developmental stages and adult tissues. By comparing these data sets with equivalent novel and previously available data for various vertebrate species, especially zebrafish, we uncovered multiple conserved and vertebrate-specific regulatory landmarks. We first identify a conserved chordate phylotypic stage, a developmental period in which different chordate species show the highest gene expression similarity. We also shed light on the origin of enhancer demethylation in vertebrates, by identifying, for the first time in an invertebrate species, differentially methylated enhancers. Furthermore, we show that conserved clusters of co-expressed and tissue-specific genes display similar enrichments for cis-regulatory motifs between amphioxus and vertebrates. Finally, we study the impact of vertebrate WGDs on the evolution of gene regulation, providing the first genome-wide quantitative assessment of sub-functionalization and neo-functionalization processes after the vertebrate WGDs; changing the way in which these evolutionary mechanisms have been traditionally understood.
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Project description:What genomic changes led to the origin of vertebrates remains a mystery. On the one hand, animal evolution is thought to be driven mostly by changes in the cis-regulatory regions of a shared conserved and toolkit of developmental genes. On the other hand, vertebrates experienced two rounds of whole genome duplication (WGD) that increased their gene repertoire, particularly of regulatory genes controlling embryo development. To shed light into the origin and evolution of the vertebrate regulatory genome, we have generated an unprecedented transcriptomic and epigenomic resource for the non-duplicated genome of the European amphioxus, a closely related invertebrate chordate. These data include RNA-seq for more than 35 developmental stages and adult tissues, CAGE-seq, ChIP-seq, bisulphite-seq and ATAC-seq for several developmental stages and adult tissues. By comparing these data sets with equivalent novel and previously available data for various vertebrate species, especially zebrafish, we uncovered multiple conserved and vertebrate-specific regulatory landmarks. We first identify a conserved chordate phylotypic stage, a developmental period in which different chordate species show the highest gene expression similarity. We also shed light on the origin of enhancer demethylation in vertebrates, by identifying, for the first time in an invertebrate species, differentially methylated enhancers. Furthermore, we show that conserved clusters of co-expressed and tissue-specific genes display similar enrichments for cis-regulatory motifs between amphioxus and vertebrates. Finally, we study the impact of vertebrate WGDs on the evolution of gene regulation, providing the first genome-wide quantitative assessment of sub-functionalization and neo-functionalization processes after the vertebrate WGDs; changing the way in which these evolutionary mechanisms have been traditionally understood.
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Project description:What genomic changes led to the origin of vertebrates remains a mystery. On the one hand, animal evolution is thought to be driven mostly by changes in the cis-regulatory regions of a shared conserved and toolkit of developmental genes. On the other hand, vertebrates experienced two rounds of whole genome duplication (WGD) that increased their gene repertoire, particularly of regulatory genes controlling embryo development. To shed light into the origin and evolution of the vertebrate regulatory genome, we have generated an unprecedented transcriptomic and epigenomic resource for the non-duplicated genome of the European amphioxus, a closely related invertebrate chordate. These data include RNA-seq for more than 35 developmental stages and adult tissues, CAGE-seq, ChIP-seq, bisulphite-seq and ATAC-seq for several developmental stages and adult tissues. By comparing these data sets with equivalent novel and previously available data for various vertebrate species, especially zebrafish, we uncovered multiple conserved and vertebrate-specific regulatory landmarks. We first identify a conserved chordate phylotypic stage, a developmental period in which different chordate species show the highest gene expression similarity. We also shed light on the origin of enhancer demethylation in vertebrates, by identifying, for the first time in an invertebrate species, differentially methylated enhancers. Furthermore, we show that conserved clusters of co-expressed and tissue-specific genes display similar enrichments for cis-regulatory motifs between amphioxus and vertebrates. Finally, we study the impact of vertebrate WGDs on the evolution of gene regulation, providing the first genome-wide quantitative assessment of sub-functionalization and neo-functionalization processes after the vertebrate WGDs; changing the way in which these evolutionary mechanisms have been traditionally understood.
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