Chromatin accessibility in the Drosophila embryo is determined by transcription factor pioneering and enhancer activation [Mnase-seq]
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ABSTRACT:
PROVIDER: PRJNA905855 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22424127_1.fastq.gz | Fastqsanger.gz | |||
| SRR22424127_2.fastq.gz | Fastqsanger.gz | |||
| SRR22424128_1.fastq.gz | Fastqsanger.gz | |||
| SRR22424128_2.fastq.gz | Fastqsanger.gz | |||
| SRR22424129_1.fastq.gz | Fastqsanger.gz |
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Project description:Spatiotemporal gene regulation during embryonic development is driven by cis-regulatory DNA sequences called enhancers. Enhancers are activated through a combination of transcription factors (TFs) that bind to short sequence motifs within these sequences, but the order of events by which TFs read out motifs is not clear. Some TFs can only bind chromatin that is already accessible, while other TFs called pioneers can open chromatin themselves. Identifying motifs and the order by which they drive chromatin accessibility is very challenging. The recent implementation of convolutional neural networks, which learn complex cis-regulatory sequence rules that are predictive for genomics data, provides an unprecedented opportunity to dissect this problem. Here, we trained base-resolution deep learning models and applied them to high-resolution TF binding and chromatin accessibility data from the well-studied early Drosophila embryo. We uncover a clear hierarchical relationship between the pioneer Zelda and the TFs involved in the spatiotemporal patterning of the embryo, consistent with Zelda being a pioneer. However, the models predict that patterning TFs can also augment chromatin accessibility in a context-specific manner. Using a series of Drosophila mutant strains, we find that the two types of TFs increase chromatin accessibility by distinct mechanisms. Zelda’s pioneering is proportional to motif affinity, while the patterning TFs specifically increase chromatin accessibility when they mediate enhancer activation. This was conclusive because Dorsal can function both as activator and repressor, and the effect on chromatin accessibility depended on Dorsal’s transactivation effect and not on its binding per se. In conclusion, chromatin accessibility occurs in two phases: one through pioneering, which makes regions first accessible but not necessarily active, and a second when the correct combination of transcription factors lead to enhancer activation.
2022-12-20 | GSE218850 | GEO
Project description:Chromatin accessibility in the Drosophila embryo is determined by transcription factor pioneering and enhancer activation
| PRJNA905853 | ENA
Project description:Chromatin accessibility in the Drosophila embryo is determined by transcription factor pioneering and enhancer activation [PBM]
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Project description:Spatiotemporal gene regulation during embryonic development is driven by cis-regulatory DNA sequences called enhancers. Enhancers are activated through a combination of transcription factors (TFs) that bind to short sequence motifs within these sequences, but the order of events by which TFs read out motifs is not clear. Some TFs can only bind chromatin that is already accessible, while other TFs called pioneers can open chromatin themselves. Identifying motifs and the order by which they drive chromatin accessibility is very challenging. The recent implementation of convolutional neural networks, which learn complex cis-regulatory sequence rules that are predictive for genomics data, provides an unprecedented opportunity to dissect this problem. Here, we trained base-resolution deep learning models and applied them to high-resolution TF binding and chromatin accessibility data from the well-studied early Drosophila embryo. We uncover a clear hierarchical relationship between the pioneer Zelda and the TFs involved in the spatiotemporal patterning of the embryo, consistent with Zelda being a pioneer. However, the models predict that patterning TFs can also augment chromatin accessibility in a context-specific manner. Using a series of Drosophila mutant strains, we find that the two types of TFs increase chromatin accessibility by distinct mechanisms. Zelda’s pioneering is proportional to motif affinity, while the patterning TFs specifically increase chromatin accessibility when they mediate enhancer activation. This was conclusive because Dorsal can function both as activator and repressor, and the effect on chromatin accessibility depended on Dorsal’s transactivation effect and not on its binding per se. In conclusion, chromatin accessibility occurs in two phases: one through pioneering, which makes regions first accessible but not necessarily active, and a second when the correct combination of transcription factors lead to enhancer activation.
2022-12-20 | GSE218851 | GEO
Project description:Chromatin accessibility in the Drosophila embryo is determined by transcription factor pioneering and enhancer activation [ATAC-seq]
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Project description:Chromatin accessibility in the Drosophila embryo is determined by transcription factor pioneering and enhancer activation [ChIP-nexus]
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Project description:Spatiotemporal gene regulation during embryonic development is driven by cis-regulatory DNA sequences called enhancers. Enhancers are activated through a combination of transcription factors (TFs) that bind to short sequence motifs within these sequences, but the order of events by which TFs read out motifs is not clear. Some TFs can only bind chromatin that is already accessible, while other TFs called pioneers can open chromatin themselves. Identifying motifs and the order by which they drive chromatin accessibility is very challenging. The recent implementation of convolutional neural networks, which learn complex cis-regulatory sequence rules that are predictive for genomics data, provides an unprecedented opportunity to dissect this problem. Here, we trained base-resolution deep learning models and applied them to high-resolution TF binding and chromatin accessibility data from the well-studied early Drosophila embryo. We uncover a clear hierarchical relationship between the pioneer Zelda and the TFs involved in the spatiotemporal patterning of the embryo, consistent with Zelda being a pioneer. However, the models predict that patterning TFs can also augment chromatin accessibility in a context-specific manner. Using a series of Drosophila mutant strains, we find that the two types of TFs increase chromatin accessibility by distinct mechanisms. Zelda’s pioneering is proportional to motif affinity, while the patterning TFs specifically increase chromatin accessibility when they mediate enhancer activation. This was conclusive because Dorsal can function both as activator and repressor, and the effect on chromatin accessibility depended on Dorsal’s transactivation effect and not on its binding per se. In conclusion, chromatin accessibility occurs in two phases: one through pioneering, which makes regions first accessible but not necessarily active, and a second when the correct combination of transcription factors lead to enhancer activation.
2022-12-20 | GSE218849 | GEO
Project description:Spatiotemporal gene regulation during embryonic development is driven by cis-regulatory DNA sequences called enhancers. Enhancers are activated through a combination of transcription factors (TFs) that bind to short sequence motifs within these sequences, but the order of events by which TFs read out motifs is not clear. Some TFs can only bind chromatin that is already accessible, while other TFs called pioneers can open chromatin themselves. Identifying motifs and the order by which they drive chromatin accessibility is very challenging. The recent implementation of convolutional neural networks, which learn complex cis-regulatory sequence rules that are predictive for genomics data, provides an unprecedented opportunity to dissect this problem. Here, we trained base-resolution deep learning models and applied them to high-resolution TF binding and chromatin accessibility data from the well-studied early Drosophila embryo. We uncover a clear hierarchical relationship between the pioneer Zelda and the TFs involved in the spatiotemporal patterning of the embryo, consistent with Zelda being a pioneer. However, the models predict that patterning TFs can also augment chromatin accessibility in a context-specific manner. Using a series of Drosophila mutant strains, we find that the two types of TFs increase chromatin accessibility by distinct mechanisms. Zelda’s pioneering is proportional to motif affinity, while the patterning TFs specifically increase chromatin accessibility when they mediate enhancer activation. This was conclusive because Dorsal can function both as activator and repressor, and the effect on chromatin accessibility depended on Dorsal’s transactivation effect and not on its binding per se. In conclusion, chromatin accessibility occurs in two phases: one through pioneering, which makes regions first accessible but not necessarily active, and a second when the correct combination of transcription factors lead to enhancer activation.
2022-12-20 | GSE218848 | GEO
Project description:Nucleosome structure and positioning play pivotal roles in gene regulation, DNA repair and other essential processes in eukaryotic cells. Nucleosomal DNA is thought to be uniformly inaccessible to DNA binding and processing factors, such as MNase. Here, we show, however, that nucleosome accessibility and sensitivity to MNase varies. Digestion of Drosophila chromatin with two distinct concentrations of MNase revealed two types of nucleosomes: sensitive and resistant. MNase-resistant nucleosome arrays are less accessible to low concentrations of MNase, whereas MNase-sensitive arrays are degraded by high concentrations. MNase-resistant nucleosomes assemble on sequences depleted of A/T and enriched in G/C containing dinucleotides. In contrast, MNase-sensitive nucleosomes form on A/T rich sequences represented by transcription start and termination sites, enhancers and DNase hypersensitive sites. Lowering of cell growth temperature to ~10°C stabilizes MNase-sensitive nucleosomes suggesting that variations in sensitivity to MNase are related to either thermal fluctuations in chromatin fiber or the activity of enzymatic machinery. In the vicinity of active genes and DNase hypersensitive sites nucleosomes are organized into synchronous, periodic arrays. These patterns are likely to be caused by “phasing” nucleosomes off a potential barrier formed by DNA-bound factors and we provide an extensive biophysical framework to explain this effect. Mnase-seq, Mnase-ChIP-seq of Drosophila melanogaster embryo and S2 cells chromatin
2015-09-17 | E-GEOD-69177 | biostudies-arrayexpress
Project description:Chromatin accessibility is integral to the process by which transcription factors (TFs) read out cis-regulatory DNA sequences, but it is difficult to differentiate between TFs that drive accessibility and those that do not. Deep learning models that learn complex sequence rules provide an unprecedented opportunity to dissect this problem. Using zygotic genome activation in Drosophila as a model, we analyzed high-resolution TF binding and chromatin accessibility data with interpretable deep learning and performed genetic validation experiments. We identify a hierarchical relationship between the pioneer TF Zelda and the TFs involved in axis patterning. Zelda consistently pioneers chromatin accessibility proportional to motif affinity, whereas patterning TFs augment chromatin accessibility in sequence contexts where they mediate enhancer activation. We conclude that chromatin accessibility occurs in two tiers: one through pioneering, which makes enhancers accessible but not necessarily active, and the second when the correct combination of TFs leads to enhancer activation.
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