Global identification of retinoic acid regulated enhancers and silencers
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ABSTRACT:
PROVIDER: PRJNA544231 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9108380.fastq.gz | Fastqsanger.gz | |||
| SRR9108390.fastq.gz | Fastqsanger.gz | |||
| SRR9108400.fastq.gz | Fastqsanger.gz | |||
| SRR9108410.fastq.gz | Fastqsanger.gz | |||
| SRR9108381.fastq.gz | Fastqsanger.gz |
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Project description:Retinoic acid (RA) is known to regulate many genes during development by acting as a ligand for nuclear RA receptors that bind RA response elements (RAREs). However, identification of RAREs required to activate or repress specific genes during development has been quite difficult. Here, we focused on identification of RAREs in the developing trunk of vertebrate embryos during the early stages of body axis extension when RA controls neuromesodermal progenitor differentiation, spinal cord neurogenesis, somitogenesis, and forelimb bud initiation. Trunks from wild-type and Aldh1a2-/- mutants lacking RA synthesis were compared using ChIP-seq analysis for H3K27ac (a marker of gene activation) and H3K27me3 (a marker of gene repression) as well as RNA-seq analysis. We identified numerous RAREs, defined as elements displaying differential deposition of H3K27ac and/or H3K27me3 marks in Aldh1a2-/- vs wild-type that contain a canonical RARE sequence and are near genes that have altered expression when RA is missing. Our findings were able to differentiate genes likely to be directly regulated by RA via a RARE versus genes regulated by another factor further downstream. We identified several RA-regulated genes associated with changes in both H3K27ac and H3K27me3 near a RARE, providing new insight into how RAREs function in vivo.
2019-05-23 | GSE131624 | GEO
Project description:Global identification of retinoic acid regulated genes
| PRJNA544092 | ENA
Project description:Enhancers and silencers often depend on the same transcription factors (TFs) and are imperfectly distinguished from each other by genomic assays of TF binding or chromatin state. To identify sequence features that define enhancers and silencers, we assayed massively parallel reporter libraries of genomic sequences targeted by the photoreceptor TF CRX and found instances of enhancer, silencer, or no activity. Both enhancers and silencers contain more TF motifs than inactive sequences, but enhancers contain motifs from a more diverse collection of TFs. We developed a measure of information content that describes the number and diversity of motifs in a sequence and found that, while both enhancers and silencers depend on CRX motifs, enhancers have higher information content. Our results indicate that enhancers contain motifs for a diverse but degenerate collection of TFs, while silencers depend on a smaller and less diverse collection of TFs.
2021-01-30 | GSE165812 | GEO
Project description:Silencers active in the Drosophila embryonic mesoderm were identified by reporter assays in dissociated embryonic cells. We find that, despite the presence of ChIP peaks for known transcriptional corepressors and marks of repressed chromatin, the only significantly enriched source of mesodermal silencers is non-mesodermal enhancers. We present evidence that a subset of silencers acts by looping to target promoters.
2019-09-25 | GSE137949 | GEO
Project description:Information Content Differentiates Enhancers From Silencers in Mouse Photoreceptors
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Project description:Retinoic acid (RA) signaling plays a major role in controlling several developmental processes in vertebrate embryos. RA repression of caudal Fgf8 has emerged as a crucial mechanism through which RA controls body axis extension, somitogenesis, and spinal cord neurogenesis. The role of RA in Fgf8 repression is supported by mechanistic studies demonstrating direct RA repression through a nearby RA response element that recruits NCOR in an RA-dependent manner. RA is also required for balanced neuromesodermal progenitor differentiation needed for coordinated generation of mesodermal progenitors for somites and neural progenitors for spinal cord. As many pathways are controlled by RA, we performed RNA-seq analysis comparing wild-type embryos with Aldh1a2 mutants that lack the ability to produce RA. This analysis identified a few hundred genes whose expression is significantly altered when RA is absent, thus providing candidate genes for further analysis to discover RA-regulated genes essential for development.
2019-05-22 | GSE131584 | GEO
Project description:This is to determine the T cell genes regulated by retinoic acid.
2011-02-14 | GSE20500 | GEO
Project description:This is to determine the T cell genes regulated by retinoic acid. 3 groups of CD4+ T cells (control, RA and Ro) 2 arrays were used for each group
2011-02-14 | E-GEOD-20500 | biostudies-arrayexpress
Project description:The aim of this study is to identify microRNAs (miRNAs) transcriptionnally regulated by retinoic acid (RA). For that purpose we have used the RA-based treatment of the Acute Promyelocytic Leukemia (APL) as a model. This malignancy is characterised by a differentiation arrest of granulopoiesis at the promyelocytic stage. APL is molecularly associated with reciprocal translocations that always involve the retinoic acid receptor a (RARa). In the vast majority of APL cases, a t(15;17) chromosomal translocation fuses the genes encoding the promyelocytic leukemia protein PML and RARa. The resulting PML-RARa is a transcriptional repressor that impedes the expression of RA-regulated genes notably through an aberrant recruitment of transcriptional repressors and histone deacetylases. Consequently, these genes become insensitive to physiological doses (nanoM) of all-trans-retinoic acid (ATRA) but pharmacological doses (microM), overcome the PML-RARa-mediated repression and restore normal transcription and granulocytic differentiation. The restorative effects of RA can be reproduced in vitro in the NB4 cells, which were derived from an APL patient. These cells provide an excellent model to study the transcriptional deregulations that arise in APL and the molecular effects of the anti-cancerous RA-based treatment. We also used in this study the RA-resistant cells, namely NB4-LR1 and NB4-LR2 cells. The NB4-LR1 cells do transcriptionally respond to ATRA but do not maturate. In contrast, the NB4-LR2 cells show a clear defect in RA signaling, as they harbor a truncated form of PML-RAR protein that is not sensitive to pharmacological doses of RA. First, we plan to characterize miRNAs-repressed by PML-RAR. We reasoned that if some miRNAs are repressed by this protein, then pharmacological doses of RA should abolish this repression and lead to an increase in the level of expression of the corresponding miRNAs. NB4, NB4-LR1 and NB4-LR2 cells will thus be treated for 16h with ATRA (1 microM), and miRNAs profiles will be compared. We anticipate that, the expression of a potential miRNA-repressed by PML-RAR should be up-regulated by ATRA in both NB4 and NB4-LR1 cells but remain unchanged in NB4-LR2 cells. This expression pattern should in fact be similar to those observed for known RA-regulated genes, such as RARb, a well characterized target of the RARa and PML-RAR proteins. Importantly, this experimental procedure was already validated with the identification of a miRNA repressed by PML-RAR (patent Lecellier et al. #WO 2006/048553). MiRNAs candidates obtained will then be validated by chromatin immunoprecipitation using anti-RARa and anti-PML antibodies, followed by luciferase assays in presence or absence of ATRA. Keywords: retinoic acid-mediated gene regulation To characterize miRNAs regulated by PML-RAR.
2008-11-17 | E-GEOD-11379 | biostudies-arrayexpress
Project description:The aim of this study is to identify microRNAs (miRNAs) transcriptionnally regulated by retinoic acid (RA). For that purpose we have used the RA-based treatment of the Acute Promyelocytic Leukemia (APL) as a model. This malignancy is characterised by a differentiation arrest of granulopoiesis at the promyelocytic stage. APL is molecularly associated with reciprocal translocations that always involve the retinoic acid receptor a (RARa). In the vast majority of APL cases, a t(15;17) chromosomal translocation fuses the genes encoding the promyelocytic leukemia protein PML and RARa. The resulting PML-RARa is a transcriptional repressor that impedes the expression of RA-regulated genes notably through an aberrant recruitment of transcriptional repressors and histone deacetylases. Consequently, these genes become insensitive to physiological doses (nanoM) of all-trans-retinoic acid (ATRA) but pharmacological doses (microM), overcome the PML-RARa-mediated repression and restore normal transcription and granulocytic differentiation. The restorative effects of RA can be reproduced in vitro in the NB4 cells, which were derived from an APL patient. These cells provide an excellent model to study the transcriptional deregulations that arise in APL and the molecular effects of the anti-cancerous RA-based treatment. We also used in this study the RA-resistant cells, namely NB4-LR1 and NB4-LR2 cells. The NB4-LR1 cells do transcriptionally respond to ATRA but do not maturate. In contrast, the NB4-LR2 cells show a clear defect in RA signaling, as they harbor a truncated form of PML-RAR protein that is not sensitive to pharmacological doses of RA. First, we plan to characterize miRNAs-repressed by PML-RAR. We reasoned that if some miRNAs are repressed by this protein, then pharmacological doses of RA should abolish this repression and lead to an increase in the level of expression of the corresponding miRNAs. NB4, NB4-LR1 and NB4-LR2 cells will thus be treated for 16h with ATRA (1 microM), and miRNAs profiles will be compared. We anticipate that, the expression of a potential miRNA-repressed by PML-RAR should be up-regulated by ATRA in both NB4 and NB4-LR1 cells but remain unchanged in NB4-LR2 cells. This expression pattern should in fact be similar to those observed for known RA-regulated genes, such as RARb, a well characterized target of the RARa and PML-RAR proteins. Importantly, this experimental procedure was already validated with the identification of a miRNA repressed by PML-RAR (patent Lecellier et al. #WO 2006/048553). MiRNAs candidates obtained will then be validated by chromatin immunoprecipitation using anti-RARa and anti-PML antibodies, followed by luciferase assays in presence or absence of ATRA. Keywords: retinoic acid-mediated gene regulation
2008-11-18 | GSE11379 | GEO