Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA274739 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1792511.fastq.gz | Fastqsanger.gz | |||
| SRR1792512.fastq.gz | Fastqsanger.gz | |||
| SRR1792513.fastq.gz | Fastqsanger.gz | |||
| SRR1792514.fastq.gz | Fastqsanger.gz | |||
| SRR1792515.fastq.gz | Fastqsanger.gz |
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Project description:We report the genome-wide binding patterns of nuclear FGFR1, RXRα and Nur77 in pluripotenet mESC and as mESC differentiate towared a neuronal lineage in response to high levels of Retinoic Acid treatment in vitro. We also report the genome-wide incorporation of histone varant H3.3 into chromatin specifically during Retinoic Acid-induced differentiation. This study presents nuclear FGFR1 as a global factor that controls genomic function by binding within the promoters of thousands of genes, both alone and in cooperation with RXR, Nur77 and histone H3.3, by targeting consensus DNA sequences of diverse transcription factor families. As such, it identifies a previously unknown, multifaceted form of control of major ontogenic pathways and gene networks targeted by the nuclear form of FGFR1.
2015-05-01 | GSE65695 | GEO
Project description:We report the genome-wide binding patterns of nuclear FGFR1, RXR? and Nur77 in pluripotenet mESC and as mESC differentiate towared a neuronal lineage in response to high levels of Retinoic Acid treatment in vitro. We also report the genome-wide incorporation of histone varant H3.3 into chromatin specifically during Retinoic Acid-induced differentiation. This study presents nuclear FGFR1 as a global factor that controls genomic function by binding within the promoters of thousands of genes, both alone and in cooperation with RXR, Nur77 and histone H3.3, by targeting consensus DNA sequences of diverse transcription factor families. As such, it identifies a previously unknown, multifaceted form of control of major ontogenic pathways and gene networks targeted by the nuclear form of FGFR1. Examination of nuclear FGFR1, RXR?, and Nur77 binding sites in 2 celluar states. Examination of H3.3 incorporation in 1 cellular state.
2015-05-01 | E-GEOD-65695 | biostudies-arrayexpress
Project description:Among its many roles in development, retinoic acid determines the anterior-posterior identity of differentiating motor neurons by activating Retinoic Acid Receptor (RAR)-mediated transcription. RAR is thought to bind the genome constitutively, and only induce transcription in the presence of the retinoid ligand. However, little is known about where RAR binds to the genome or how it selects target sites. We tested the constitutive RAR binding model using the retinoic acid-driven differentiation of mouse embryonic stem cells into differentiated motor neurons. We find that retinoic acid treatment results in widespread changes in RAR genomic binding, including novel binding to genes directly responsible for anterior-posterior specification, as well as the subsequent recruitment of the basal polymerase machinery. Finally, we discovered that the binding of transcription factors at the embryonic stem cell stage can accurately predict where in the genome RAR binds after initial differentiation. We have characterized a ligand-dependent shift in RAR genomic occupancy at the initiation of neurogenesis. Our data also suggests that enhancers active in pluripotent embryonic stem cells may be preselecting regions that will be activated by RAR during neuronal differentiation. The differentiation of ventral motor neurons is induced by treating embryonic stem cell cultures with retinoic acid. Here, ChIP-seq is used to profile the genome-wide occupancy of RAR isofroms both immediately prior to and during exposure of the cells to retinoic acid. ChIP-seq is also used to profile the genomic occupancy of Pol2 with phosphorylated serine 5 (Pol2-S5P) and phosphorylated serine 2 (Pol2-S2P) after exposure to retinoic acid.
2010-12-10 | E-GEOD-19409 | biostudies-arrayexpress
Project description:Among its many roles in development, retinoic acid determines the anterior-posterior identity of differentiating motor neurons by activating Retinoic Acid Receptor (RAR)-mediated transcription. RAR is thought to bind the genome constitutively, and only induce transcription in the presence of the retinoid ligand. However, little is known about where RAR binds to the genome or how it selects target sites. We tested the constitutive RAR binding model using the retinoic acid-driven differentiation of mouse embryonic stem cells into differentiated motor neurons. We find that retinoic acid treatment results in widespread changes in RAR genomic binding, including novel binding to genes directly responsible for anterior-posterior specification, as well as the subsequent recruitment of the basal polymerase machinery. Finally, we discovered that the binding of transcription factors at the embryonic stem cell stage can accurately predict where in the genome RAR binds after initial differentiation. We have characterized a ligand-dependent shift in RAR genomic occupancy at the initiation of neurogenesis. Our data also suggests that enhancers active in pluripotent embryonic stem cells may be preselecting regions that will be activated by RAR during neuronal differentiation.
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Project description:In mouse embryonic cells, a retinoic acid (RA) stimulation triggers a massive change of gene expression leading the pluripotent, proliferating cells to a lineage-specific differentiation process. The retinoic acid receptor (RAR) plays a key role in this response by inhibiting pluripotency-maintaining genes and simultaneously activating some major actors of cell differentiation. To investigate the mechanism underlying this dual regulation, we performed joint RAR/RXR ChIP-seq and mRNA-seq time series during the first 48 hours of the RA-induced Primitive Endoderm differentiation process in F9 embryonic carcinoma cells. We detected significantly more RAR/RXR binding regions than previous studies and identified among them a handful of typical binding intensity patterns during differentiation. We demonstrate that these patterns are correlated with the coincidental binding of essential transcription factors (TFs) for pluripotency maintenance or PrE differentiation of embryonic stem (ES) cells, as well as the presence of variants of RAR binding motifs. Most importantly, early-bound regions coincide with pluripotency-associated transcription factor binding in ES (like Pou5f1, Sox2, Esrrb and Nr5a2) and display an increased frequency of the DR0 type RAR binding motifs; late-bound sites are associated to the PrE marker Sox17 and are enriched in the canonical DR5 binding motif. Our data offer an unprecedently detailed view on the action of RA in triggering pluripotent cell differentiation. Altogether, this work sheds light on the relocation of RAR/RXR binding sites throughout differentiation, and shows how RAR/RXR progressively shift from DR0 enriched regions, which were specifically identified in undifferentiated models, to canonical RAR binding sites containing loci. Time course (0, 2, 6, 12, 24, 48h) after stimulation of F9 cultured cells by retinoic acid: PanRAR and PanRXR ChIP-seq at 0, 2, 24 and 48h (no replicate); WCE-seq at 0h (no replicate); mRNA-seq at 0, 6, 12, 24, 48h (2 replicates except for time 0h, 4 replicates). Additionally, a control time course (culture in DMSO) sampled at 24 and 48h (no replicates).
2015-04-17 | E-GEOD-56893 | biostudies-arrayexpress
Project description:Pluripotent mouse Embryonic Stem Cells and during Retinoic Acid-induced differentiation
| PRJNA274737 | ENA
Project description:Haffez2017 - RAR interaction with synthetic
analogues
This model is described in the article:
The molecular basis of the
interactions between synthetic retinoic acid analogues and the
retinoic acid receptors
Hesham Haffez, David R. Chisholm,
Roy Valentine, Ehmke Pohl, Christopher Redfern and Andrew
Whiting
MedChemComm
Abstract:
All-trans-retinoic acid (ATRA) and its synthetic analogues
EC23 and EC19 direct cellular differentiation by interacting as
ligands for the retinoic acid receptor (RARα,
β and γ) family of nuclear receptor
proteins. To date, a number of crystal structures of natural
and synthetic ligands complexed to their target proteins have
been solved, providing molecular level snap-shots of ligand
binding. However, a deeper understanding of receptor and ligand
flexibility and conformational freedom is required to develop
stable and effective ATRA analogues for clinical use.
Therefore, we have used molecular modelling techniques to
define RAR interactions with ATRA and two synthetic analogues,
EC19 and EC23, and compared their predicted biochemical
activities to experimental measurements of relative ligand
affinity and recruitment of coactivator proteins. A
comprehensive molecular docking approach that explored the
conformational space of the ligands indicated that ATRA is able
to bind the three RAR proteins in a number of conformations
with one extended structure being favoured. In contrast the
biologically-distinct isomer, 9-cis-retinoic acid (9CRA),
showed significantly less conformational flexibility in the RAR
binding pockets. These findings were used to inform docking
studies of the synthetic retinoids EC23 and EC19, and their
respective methyl esters. EC23 was found to be an excellent
mimic for ATRA, and occupied similar binding modes to ATRA in
all three target RAR proteins. In comparison, EC19 exhibited an
alternative binding mode which reduces the strength of key
polar interactions in RARα/γ but is
well-suited to the larger RARβ binding pocket. In
contrast, docking of the corresponding esters revealed the loss
of key polar interactions which may explain the much reduced
biological activity. Our computational results were
complemented using an in vitro binding assay based on FRET
measurements, which showed that EC23 was a strongly binding,
pan-agonist of the RARs, while EC19 exhibited specificity for
RARβ, as predicted by the docking studies. These
findings can account for the distinct behaviour of EC23 and
EC19 in cellular differentiation assays, and additionally, the
methods described herein can be further applied to the
understanding of the molecular basis for the selectivity of
different retinoids to RARα, β and
γ.
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2024-09-02 | BIOMD0000000629 | BioModels
Project description:In mouse embryonic cells, a retinoic acid (RA) stimulation triggers a massive change of gene expression leading the pluripotent, proliferating cells to a lineage-specific differentiation process. The retinoic acid receptor (RAR) plays a key role in this response by inhibiting pluripotency-maintaining genes and simultaneously activating some major actors of cell differentiation. To investigate the mechanism underlying this dual regulation, we performed joint RAR/RXR ChIP-seq and mRNA-seq time series during the first 48 hours of the RA-induced Primitive Endoderm differentiation process in F9 embryonic carcinoma cells. We detected significantly more RAR/RXR binding regions than previous studies and identified among them a handful of typical binding intensity patterns during differentiation. We demonstrate that these patterns are correlated with the coincidental binding of essential transcription factors (TFs) for pluripotency maintenance or PrE differentiation of embryonic stem (ES) cells, as well as the presence of variants of RAR binding motifs. Most importantly, early-bound regions coincide with pluripotency-associated transcription factor binding in ES (like Pou5f1, Sox2, Esrrb and Nr5a2) and display an increased frequency of the DR0 type RAR binding motifs; late-bound sites are associated to the PrE marker Sox17 and are enriched in the canonical DR5 binding motif. Our data offer an unprecedently detailed view on the action of RA in triggering pluripotent cell differentiation. Altogether, this work sheds light on the relocation of RAR/RXR binding sites throughout differentiation, and shows how RAR/RXR progressively shift from DR0 enriched regions, which were specifically identified in undifferentiated models, to canonical RAR binding sites containing loci.
2015-04-17 | GSE56893 | GEO
Project description:Retinoic acid (RA) plays a pivotal role in different biological processes including inducing differentiation of embryonic stem cells (ESCs). We first knocked out one or both of RA receptors- Rarα and Rxrα to partially abolish the RA signaling, and then overexpressed one of them separately to hyper activation of RA signaling pathway. By transcriptome analysis, we show that RA signaling effects multi-lineage differentiation, particularly the endoderm, and identify RA signaling target genes, interesting, there are two family cluster genes- Hoxb and Cyp26. Chromosome immunoprecipitation (ChIP-seq) shows that RA induces novel proximal and distal enhancers around the cluster target genes and these enhancers are dependent of RA receptors(Rarα/Rxrα). 4C-seq reveals enhancer-enhancer and enhancer-promoter interactions in their regions and shows a decrease in the relative frequency of contact relative to WT after Rarα/Rxrα-knockout, suggesting Rarα/Rxrα participate in mediating chromatin interaction. We also identify that enhancers significantly maintain expression of RA-induced Hoxb and Cyp26 family genes and regulate multi-lineage marker genes. At the same time, we reveal that disrupting RA-response elements (RAREs) in the enhancer affects the expression of the target gene. Our study provides mechanistic insight into RA-induced early ESC differentiation to endoderm and potential regular regulation of downstream target genes.
2023-06-29 | GSE221992 | GEO
Project description:Expression profile of miRNAs during retinoic acid (RA) induced differentiation of mose embryonic stem cells Expression profile of mRNAs during retinoic acid (RA) amd miR-134 induced differentiation of mouse embryonic stem cells. Keywords: affymetrix custom array and illumina MouseRef-8
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