Global identification of retinoic acid regulated enhancers and silencers
Ontology highlight
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:Differential gene transcription enables development and homeostasis in all animals and is regulated by two major classes of distal cis-regulatory DNA elements (CREs), enhancers and silencers. While enhancers have been thoroughly characterized, the properties and mechansisms of silencers remain largely unknown. By an unbiased genome-wide functional screen in Drosophila melanogaster S2 cells, we discover a class of silencers that bind one of three transcription factors (TFs) and are generally not included in chromatin-defined CRE catalogs, as they mostly lack detectable DNA accessibility. The silencer-binding TF CG11247, which we term Saft, safeguards cell fate decisions in vivo and functions via a highly-conserved domain we term ZAC and the corepressor G9a, independently of G9a’s H3K9-methyltransferase activity. Overall, our identification of silencers with unexpected properties and mechanisms has important implications for the understanding and future study of repressive CREs, as well as the functional annotation of animal genomes.
2024-11-13 | PXD047987 | Pride
Project description:Differential gene transcription enables development and homeostasis in all animals and is regulated by two major classes of distal cis-regulatory DNA elements (CREs), enhancers and silencers. While enhancers have been thoroughly characterized, the properties and mechansisms of silencers remain largely unknown. By an unbiased genome-wide functional screen in Drosophila melanogaster S2 cells, we discover a class of silencers that bind one of three transcription factors (TFs) and are generally not included in chromatin-defined CRE catalogs, as they mostly lack detectable DNA accessibility. The silencer-binding TF CG11247, which we term Saft, safeguards cell fate decisions in vivo and functions via a highly-conserved domain we term ZAC and the corepressor G9a, independently of G9a’s H3K9-methyltransferase activity. Overall, our identification of silencers with unexpected properties and mechanisms has important implications for the understanding and future study of repressive CREs, as well as the functional annotation of animal genomes.
2024-11-13 | PXD048161 | Pride
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: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:Information Content Differentiates Enhancers From Silencers in Mouse Photoreceptors
| PRJNA697959 | ENA
Project description:Silencers, the yin to enhancers' yang, play a pivotal role in fine-tuning gene expression throughout the genome. However, despite their recognized importance, comprehensive identification of these regulatory elements in the genome is still in its early stages. We developed a method called Ss-STARR-seq to directly determine the activity of silencers in the whole genome. In this study, we applied Ss-STARR-seq to human cell lines K562, LNCaP, and 293T, and identified 134,171, 137,753, and 125,307 silencers on a genome-wide scale, respectively, these silencers function in various cells in a cell-specific manner. Silencers exhibited a substantial enrichment of transcriptional-inhibitory motifs, including REST, and demonstrated overlap with the binding sites of repressor transcription factors within the endogenous environment. Interestingly, H3K27me3 did not reflect silencer activity but facilitated the silencer's inhibitory role on gene expression. Additionally, the silencer did not have any significant histone markers at the genome-wide level. Our findings unveil that aspect-silencers not only transition into enhancers throughout diverse cell lines but also achieve functional conversion with insulators. Regarding to biological effects, knockout experiments underscored the functional redundancy and specificity of silencers in regulating gene expression and cell proliferation. In summary, this study pioneers the elucidation of the genome-wide silencer landscape in human cells, delineates their global regulatory features, and identifies specific silencers influencing cancer cell proliferation.
2024-12-06 | GSE283488 | GEO