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SRP135823
Mus musculus
5 Downloadable Samples
Illumina HiSeq 2000
Description
Trophoblast stem (TS) cells derived from the trophectoderm (TE) of mammalian embryos have the ability to self-renew indefinitely or differentiate into fetal lineages of the placenta. Epigenetic control of gene expression plays an instrumental role in dictating the fate of TS cell self-renewal and differentiation. However, the roles of histone demethylases and activating histone modifications such as methylation of histone 3 lysine 4 (H3K4me3/me2) in regulating TS cell expression programs, and in priming the epigenetic landscape for trophoblast differentiation, are largely unknown. Here, we demonstrate that the H3K4 demethylase, KDM5B, regulates the H3K4 methylome and expression landscapes of TS cells. Depletion of KDM5B resulted in downregulation of TS cell self-renewal genes and upregulation of trophoblast-lineage genes, which was accompanied by altered H3K4 methylation. Moreover, we found that KDM5B resets the H3K4 methylation landscape during differentiation in the absence of the external self-renewal signal, FGF4, by removing H3K4 methylation from promoters of self-renewal genes, and of genes whose expression is enriched in TS cells. Altogether, our data indicate an epigenetic role for KDM5B in regulating H3K4 methylation in TS cells and during trophoblast differentiation. Overall design: RNA-Seq of undifferentiated and differentiated murine shLuc and Kdm5b TS cells
Publication Title
KDM5B decommissions the H3K4 methylation landscape of self-renewal genes during trophoblast stem cell differentiation.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 14 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Trophoblast stem cells (TS cells), derived from the trophectoderm (TE) of blastocysts, require transcription factors (TFs) and external signals (Fgf4, Activin/Nodal/Tgfb) for self-renewal. While many reports have focused on TF networks that regulate embryonic stem cell (ES cell) self-renewal and pluripotency, little is know about TF networks that regulate self-renewal in TS cells. To further understand transcriptional networks in TS cells we used chromatin immunopreciptiation and DNA microarray analysis (ChIP-chip) to investigate targets of TFs Ap-2g (Tcfap2c), Eomes, Ets2, and Gata3, and a chromatin remodeling factor, Brg1 (Smarca4). We then evaluated the transcriptional states of target genes using transcriptome analysis and genome-wide analysis of histone H3 acetylation (AcH3). Our results describe previously unknown transcriptional networks in TS cells, including TF occupancy of genes involved in ES cell self-renewal and pluripotency, co-occupancy of multiple TFs at target genes, and transcriptional regulatory circuitry within the 5 factors. Through genome-wide mapping and global expression analysis of 5 TF target genes, our data provide a comprehensive analysis of transcriptional networks that regulate TS cell self-renewal.
Publication Title
Examination of transcriptional networks reveals an important role for TCFAP2C, SMARCA4, and EOMES in trophoblast stem cell maintenance.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Epigenetic regulation of gene expression is important in maintaining self-renewal of embryonic stem (ES) cells and trophoblast stem (TS) cells. Histone deacetylases (HDACs) negatively control histone acetylation by removing covalent acetylation marks from histone tails. Because histone acetylation is a known mark for active transcription, HDACs presumably associate with inactive genes. Here, we used genome-wide chromatin immunoprecipitation to investigate targets of HDAC1 in ES cells and TS cells. Through evaluation of genes associated with acetylated histone H3 marks, and global expression analysis of Hdac1 knockout ES cells and trichostatin A treated ES cells and TS cells, we found that HDAC1 occupies mainly active genes, including important regulators of ES cell and TS cell self-renewal. By mapping HDAC1 targets on a global scale, our results describe further insight into epigenetic mechanisms of ES cell and TS cell self-renewal.
Publication Title
HDAC1 regulates pluripotency and lineage specific transcriptional networks in embryonic and trophoblast stem cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina HiSeq 2000
Description
Pluripotency of embryonic stem (ES) cells is controlled in part by chromatin-modifying factors that regulate histone H3 lysine 4 (H3K4) methylation. However, it remains unclear how H3K4 demethylation contributes to ES cell function. Here, we show that KDM5B, which demethylates lysine 4 of histone H3, co-localizes with H3K4me3 near promoters and enhancers of active genes in ES cells; its depletion leads to spreading of H3K4 methylation into gene bodies and enhancer shores, indicating that KDM5B functions to focus H3K4 methylation at promoters and enhancers. Spreading of H3K4 methylation to gene bodies and enhancer shores is linked to defects in gene expression programs and enhancer activity, respectively, during self-renewal and differentiation of KDM5B-depleted ES cells. KDM5B critically regulates H3K4 methylation at bivalent genes during differentiation in the absence of LIF or Oct4. We also show that KDM5B and LSD1, another H3K4 demethylase, co-regulate H3K4 methylation at active promoters but they retain distinct roles in demethylating gene body regions and bivalent genes. Our results provide global and functional insight into the role of KDM5B in regulating H3K4 methylation marks near promoters, gene bodies, and enhancers in ES cells and during differentiation. Overall design: RNA-Seq of murine shLuc and shKdm5b ES cells differentiated for 72h in the absence of LIF.
Publication Title
KDM5B focuses H3K4 methylation near promoters and enhancers during embryonic stem cell self-renewal and differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
- Illumina HiSeq 2000
Description
Epigenetic regulation of chromatin states is thought to control the self-renewal and differentiation of embryonic stem (ES) cells. However, the roles of repressive histone modifications such as trimethylated histone lysine 20 (H4K20me3) in pluripotency and development are largely unknown. Here, we show that the histone lysine methyltransferase SMYD5 mediates H4K20me3 at heterochromatin regions. Depletion of SMYD5 leads to compromised self-renewal, including dysregulated expression of OCT4 targets, and perturbed differentiation. SMYD5 bound regions are enriched with repetitive DNA elements. Knockdown of SMYD5 results in a global decrease of H4K20me3 levels, a redistribution of heterochromatin constituents including H3K9me3/2, G9a, and HP1a, and de-repression of endogenous retroelements. A loss of SMYD5-dependent silencing of heterochromatin nearby genic regions leads to upregulated expression of lineage-specific genes, thus contributing to the decreased self-renewal and accelerated differentiation of SMYD5-depeleted ES cells. Altogether, these findings implicate a role for SMYD5 in regulating ES cell self-renewal and H4K20me3-marked heterochromatin. Overall design: RNA-Seq of undifferentiated and differentiated murine shLuc and shSmyd5 ES cells
Publication Title
SMYD5 regulates H4K20me3-marked heterochromatin to safeguard ES cell self-renewal and prevent spurious differentiation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus, Rattus norvegicus
- 21 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Rat Expression 230A Array (rae230a)
Description
We compare the transcriptome of embryonic stem cells (ESCs), adult stem cells with apparent greater differentiation potential such as multipotent adult progenitor cells (MAPCs), mesenchymal stem cells (MSCs) and neurospheres (NS). Mouse and rat MAPCs were used in this study and two different array platforms (Affymetrix and NIA) were used for mouse samples.
Publication Title
Comparative transcriptome analysis of embryonic and adult stem cells with extended and limited differentiation capacity.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 16 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The Mediator complex is an evolutionary conserved multiprotein complex that plays an essential role in initiating and regulating transcription. Its function is to act as a universal adaptor between RNA Polymerase II and DNA-bound transcription factors to translate regulatory information from activators and repressors to the transcriptional machinery. We have found that the PFT1 gene (which encodes the MED25 subunit of the Mediator complex) is required for the uncompromised expression of both salicylic acid- and jasmonate-dependent defense genes as well as resistance to the leaf-infecting fungal pathogens, Alternaria brassicicola and Botrytis cinerea in Arabidopsis. Surprisingly, we found that the pft1/med25 mutant showed increased resistance to the root infecting pathogen Fusarium oxysporum and that this resistance was independent of classical defense genes. In addition, the over-expression of PFT1 led to increased susceptibility to F. oxysporum. Therefore, to explore this phenomenon further, we wished to use whole genome transcript profiling to identify which genes may be playing a role in pft1/med25-mediated resistance to F. oxysporum.
Publication Title
The mediator complex subunit PFT1 is a key regulator of jasmonate-dependent defense in Arabidopsis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Accurate and reproducible quantitation of target genes depends on correct normalization. Historically, genes with variable tissue transcription e.g. GAPDH, have been used as normalization factors which is problematic, particularly in clinical samples which often are derived from different tissue sources. Using a large-scale gene database (GeneChip (Affymetrix U133A) dataset of 36 gastrointestinal tumors and normal tissues), we identified 8 candidate reference genes that were highly expressed with low variability and established expression levels by real-time RT-PCR in an independent set of GI tissue samples (n=42).
Publication Title
GeneChip, geNorm, and gastrointestinal tumors: novel reference genes for real-time PCR.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 27 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The transcription factor ABI4 Is required for the ascorbic acid-dependent regulation of growth and regulation of jasmonate-dependent defense signaling pathways in Arabidopsis.
Sample Metadata Fields
Age, Specimen part
View Samples- Arabidopsis thaliana
- 17 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The role of abscisic acid (ABA) signalling in the ascorbic acid (AA)-dependent control of plant growth and defence was determined using the vtc1 and vtc2 mutants, which have impaired ascorbic acid synthesis, and in the abi4 mutant that is impaired in ABA-signalling. ABA levels were increase in the mutants relative to the wild type (Col0). Like vtc1 the vtc2 mutants have a slow growth relative to Col0. However, the wild type phenotype is restored in the abi4vtc2 double mutant. Similarly, the sugar sensing phenotype of in the abi4 is reversed in the abi4vtc2 double mutant. The vtc1 and vtc2 leaf transcriptomes show up to 70 % homology with abi4. Of the transcripts that are altered in the mutants a relative to Col0, only a small number are reversed in the abi4vtc2 double mutants relative to either abi4 or vtc2. We conclude that AA controls growth via an ABA and abi4-dependent signalling pathway. The vtc and abi4 mutants have enhanced glutathione levels and common redox signalling pathways leading to similar gene expression patterns.
Publication Title
The transcription factor ABI4 Is required for the ascorbic acid-dependent regulation of growth and regulation of jasmonate-dependent defense signaling pathways in Arabidopsis.
Sample Metadata Fields
Age, Specimen part
View Samples