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SRP164732
Mus musculus
73 Downloadable Samples
Illumina HiSeq 2500
Description
The molecular regulation of zygotic genome activation (ZGA) in mammals remains poorly understood. Primed mouse embryonic stem cells contain a rare subset of “2C-like” cells that are epigenetically and transcriptionally similar to the two cell embryo and thus represent an ideal system for studying ZGA transcription regulation. Recently, the transcription factor Dux, expressed exclusively in the minor wave of ZGA, was described to activate many downstream ZGA transcripts. However, it remains unknown what upstream maternal factors initiate ZGA either in a Dux dependent or independent manner. Here we performed a candidate-based overexpression screen, identifying, amongst others, Developmental Pluripotency Associated 2 (Dppa2) and 4 (Dppa4) as positive regulators of 2C-like cells and ZGA transcription. In the germ line, promoter DNA demethylation coincides with upregulation of Dppa2 and Dppa4 which remain expressed until E7.5 when their promoters are remethylated. Furthermore, Dppa2 and Dppa4 are also expressed during iPSC reprogramming at the time 2C-like ZGA transcription transiently peaks. Through a combination of overexpression, knockdown, knockout and rescue experiments, together with transcriptional analyses, we show that Dppa2 and Dppa4 directly regulate the 2C-like cell population and associated transcripts, including Dux and the Zscan4 cluster. Importantly, we tease apart the molecular hierarchy in which the 2C-like transcriptional program is initiated and stabilised. Dppa2 and Dppa4 require Dux to initiate 2C-like ZGA transcription, suggesting they act upstream by directly regulating Dux. Supporting this, ChIP-seq analysis revealed Dppa2 and Dppa4 bind to the Dux promoter and gene body and drive its expression. Zscan4c is also able to induce 2C-like cells in wild type cells, but, in contrast to Dux, can no longer do so in Dppa2/4 double knockout cells, suggesting it may act to stabilise rather than drive the transcriptional network. Our findings suggest a model in which Dppa2/4 binding to the Dux promoter leads to Dux upregulation and activation of the 2C-like transcriptional program which is subsequently reinforced by Zscan4c. Overall design: RNA sequencing of screen hits (3 biological replicates of GFP+ and GFP- sorted cells for each of 12 candidates).
Publication Title
Dppa2 and Dppa4 directly regulate the Dux-driven zygotic transcriptional program.
Alternate Accession IDs
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 2500
Description
The molecular regulation of zygotic genome activation (ZGA) in mammals remains poorly understood. Primed mouse embryonic stem cells contain a rare subset of “2C-like” cells that are epigenetically and transcriptionally similar to the two cell embryo and thus represent an ideal system for studying ZGA transcription regulation. Recently, the transcription factor Dux, expressed exclusively in the minor wave of ZGA, was described to activate many downstream ZGA transcripts. However, it remains unknown what upstream maternal factors initiate ZGA either in a Dux dependent or independent manner. Here we performed a candidate-based overexpression screen, identifying, amongst others, Developmental Pluripotency Associated 2 (Dppa2) and 4 (Dppa4) as positive regulators of 2C-like cells and ZGA transcription. In the germ line, promoter DNA demethylation coincides with upregulation of Dppa2 and Dppa4 which remain expressed until E7.5 when their promoters are remethylated. Furthermore, Dppa2 and Dppa4 are also expressed during iPSC reprogramming at the time 2C-like ZGA transcription transiently peaks. Through a combination of overexpression, knockdown, knockout and rescue experiments, together with transcriptional analyses, we show that Dppa2 and Dppa4 directly regulate the 2C-like cell population and associated transcripts, including Dux and the Zscan4 cluster. Importantly, we tease apart the molecular hierarchy in which the 2C-like transcriptional program is initiated and stabilised. Dppa2 and Dppa4 require Dux to initiate 2C-like ZGA transcription, suggesting they act upstream by directly regulating Dux. Supporting this, ChIP-seq analysis revealed Dppa2 and Dppa4 bind to the Dux promoter and gene body and drive its expression. Zscan4c is also able to induce 2C-like cells in wild type cells, but, in contrast to Dux, can no longer do so in Dppa2/4 double knockout cells, suggesting it may act to stabilise rather than drive the transcriptional network. Our findings suggest a model in which Dppa2/4 binding to the Dux promoter leads to Dux upregulation and activation of the 2C-like transcriptional program which is subsequently reinforced by Zscan4c. Overall design: RNA-sequencing of ESCs treated with control, Dppa2 or Dppa4 siRNAs for 4 days.
Publication Title
Dppa2 and Dppa4 directly regulate the Dux-driven zygotic transcriptional program.
Alternate Accession IDs
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 7 Downloadable Samples
- Illumina HiSeq 2500
Description
The molecular regulation of zygotic genome activation (ZGA) in mammals remains poorly understood. Primed mouse embryonic stem cells contain a rare subset of “2C-like” cells that are epigenetically and transcriptionally similar to the two cell embryo and thus represent an ideal system for studying ZGA transcription regulation. Recently, the transcription factor Dux, expressed exclusively in the minor wave of ZGA, was described to activate many downstream ZGA transcripts. However, it remains unknown what upstream maternal factors initiate ZGA either in a Dux dependent or independent manner. Here we performed a candidate-based overexpression screen, identifying, amongst others, Developmental Pluripotency Associated 2 (Dppa2) and 4 (Dppa4) as positive regulators of 2C-like cells and ZGA transcription. In the germ line, promoter DNA demethylation coincides with upregulation of Dppa2 and Dppa4 which remain expressed until E7.5 when their promoters are remethylated. Furthermore, Dppa2 and Dppa4 are also expressed during iPSC reprogramming at the time 2C-like ZGA transcription transiently peaks. Through a combination of overexpression, knockdown, knockout and rescue experiments, together with transcriptional analyses, we show that Dppa2 and Dppa4 directly regulate the 2C-like cell population and associated transcripts, including Dux and the Zscan4 cluster. Importantly, we tease apart the molecular hierarchy in which the 2C-like transcriptional program is initiated and stabilised. Dppa2 and Dppa4 require Dux to initiate 2C-like ZGA transcription, suggesting they act upstream by directly regulating Dux. Supporting this, ChIP-seq analysis revealed Dppa2 and Dppa4 bind to the Dux promoter and gene body and drive its expression. Zscan4c is also able to induce 2C-like cells in wild type cells, but, in contrast to Dux, can no longer do so in Dppa2/4 double knockout cells, suggesting it may act to stabilise rather than drive the transcriptional network. Our findings suggest a model in which Dppa2/4 binding to the Dux promoter leads to Dux upregulation and activation of the 2C-like transcriptional program which is subsequently reinforced by Zscan4c. Overall design: RNA-sequencing of Dppa2 and/or Dppa4 knockout ESCs.
Publication Title
Dppa2 and Dppa4 directly regulate the Dux-driven zygotic transcriptional program.
Alternate Accession IDs
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
A complex interplay between ethylene, ETP1/ETP2 F-box proteins, and degradation of EIN2 is essential for triggering ethylene responses in plants.
Publication Title
Interplay between ethylene, ETP1/ETP2 F-box proteins, and degradation of EIN2 triggers ethylene responses in Arabidopsis.
Alternate Accession IDs
Sample Metadata Fields
Age, Treatment
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The synthetic glucocorticoids prednisolone and dexamethasone regulate the same genes in acute lymphoblastic leukemia cells.
Alternate Accession IDs
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Background: Glucocorticoids (GCs) cause apoptosis in malignant cells of lymphoid lineage by transcriptionally regulating a plethora of genes. As a result, GCs are included in almost all treatment protocols for lymphoid malignancies, particularly childhood acute lymphoblastic leukemia (chALL). The most commonly used synthetic GCs in the clinical setting are prednisolone and dexamethasone. While the latter has a higher activity and more effectively reduces the tumor load in patients, it is also accompanied by more serious adverse effects than the former. Whether this difference might be explained by regulation of different genes by the two GCs has never been addressed.
Publication Title
The synthetic glucocorticoids prednisolone and dexamethasone regulate the same genes in acute lymphoblastic leukemia cells.
Alternate Accession IDs
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Background: Glucocorticoids (GCs) cause apoptosis in malignant cells of lymphoid lineage by transcriptionally regulating a plethora of genes. As a result, GCs are included in almost all treatment protocols for lymphoid malignancies, particularly childhood acute lymphoblastic leukemia (chALL). The most commonly used synthetic GCs in the clinical setting are prednisolone and dexamethasone. While the latter has a higher activity and more effectively reduces the tumor load in patients, it is also accompanied by more serious adverse effects than the former. Whether this difference might be explained by regulation of different genes by the two GCs has never been addressed.
Publication Title
The synthetic glucocorticoids prednisolone and dexamethasone regulate the same genes in acute lymphoblastic leukemia cells.
Alternate Accession IDs
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
Description
Organoids derived from human pluripotent stem cells recapitulate the early three-dimensional organization of human brain, but whether they establish the epigenomic and transcriptional programs essential for brain development is unknown. We compared epigenomic and gene regulatory features in cerebral organoids and human fetal brain, using genome-wide, base resolution DNA methylome and transcriptome sequencing. Transcriptomic dynamics in organoids faithfully modeled gene expression trajectories in early-to-mid human fetal brains. We found that early non-CG methylation accumulation at super-enhancers in both fetal brain and organoids marks forthcoming transcriptional repression in the fully developed brain. 74% of 35,627 demethylated regions identified during organoid differentiation overlapped with fetal brain regulatory elements. Interestingly, pericentromeric repeats showed widespread demethylation in multiple types of in vitro human neural differentiation models but not in fetal brain. Our study reveals that organoids recapitulate many epigenomic features of mid-fetal human brain and also identified novel non-CG methylation signatures of brain development. Overall design: MethylC-seq and RNA-seq of Cerebral Organoids differentiation
Publication Title
Cerebral Organoids Recapitulate Epigenomic Signatures of the Human Fetal Brain.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 42 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
ACC Synthase (ACS) is the key regulatory enzyme in the ethylene biosynthesis in plants. It catalyzes the conversion of s-adenosylmethionine (SAM) to 1-aminocyclopropane-1-carboxylic acid (ACC), the precursor of ethylene. Arabidopsis has nine ACS genes. The goal of the project is to inactivate each gene by insertional mutagenesis and amiRNA technology and eventually construct a null ACS mutant. We have been recently able to achieve this goal. Furthermore, we wanted to know how inactivation of individual ACS genes affects global gene expression.
Publication Title
A combinatorial interplay among the 1-aminocyclopropane-1-carboxylate isoforms regulates ethylene biosynthesis in Arabidopsis thaliana.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
SupT1, PBMC, or IMR90 cells were infected with an HIV-based vector (see Schroder et al., Cell 110:521-9) and the RNA isolated 48 hours after infection.
Publication Title
Retroviral DNA integration: ASLV, HIV, and MLV show distinct target site preferences.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples