Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Global identification of retinoic acid regulated enhancers and silencers

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE131624 | GEO | 2019/05/23

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

RA-dependent proximal and distal enhancers’ architecture promotes RA-induced early ESC differentiation

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

Relocalization of retinoic acid receptors from non-canonical to canonical spaced binding elements during embryoid body differentiation

Project description:Retinoic Acid Receptors (RARs) bind RA-response elements in regulatory regions of their target genes. While canonical RAREs comprise direct repeats of the consensus 5’-RGKTCA-3’ sequence separated by 1, 2 or 5 nucleotides (DR1, DR2, DR5), we show that shortly after RA treatement of mouse embryoid bodies or F9 cells, RARs occupy a large repertoire of DR0, DR2, DR5, DR8 and IR0 elements. In vitro, RAR-RXR bind these non-canonical spacings with comparable affinities to DR2 and DR5. Most DR8 elements comprise three half sites with DR2 and DR0 spacings. This specific half site organisation constitutes a previously unrecognised, but frequent signature of RAR binding elements and acts as an RARE. At later stages of embryoid body differentiation, RARs relocalise to a restricted repertoire of sites comprising predominantly DR5 elements. Differentiation thus involves genomic relocalisation of RARs, and a switch from DR0 and DR8 at early times to DR5 at later stages. Examination of genomic localisation of RAR in differentiating embryoid bodies.

2012-06-15 | E-GEOD-35599 | biostudies-arrayexpress

Relocalization of retinoic acid receptors from non-canonical to canonical spaced binding elements during embryoid body differentiation

2012-06-15 | GSE35599 | GEO

Global identification of retinoic acid regulated genes

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

Chromatin state signatures associated with tissue-specific gene expression and enhancer activity in the embryonic limb.

Project description:The regulatory elements that direct tissue-specific gene expression in the developing mammalian embryo remain largely unknown. Although chromatin profiling has proven to be a powerful method for mapping regulatory sequences in cultured cells, chromatin states characteristic of active developmental enhancers have not been directly identified in embryonic tissues. Here we use whole transcriptome analysis coupled with genome-wide profiling of H3K27ac and H3K27me3 to map chromatin states and enhancers in mouse embryonic forelimb and hindlimb. We show that gene expression differences between forelimb and hindlimb, and between limb and other embryonic cell types, are correlated with tissue-specific H3K27ac signatures at promoters and distal sites. Using H3K27ac profiles, we identified 28,377 putative enhancers, many of which are likely to be limb-specific based on strong enrichment near genes highly expressed in the limb and comparisons with tissue-specific p300 sites and known enhancers. We describe a chromatin state signature associated with active developmental enhancers, defined by high levels of H3K27ac marking, nucleosome displacement, hypersensitivity to sonication, and strong depletion of H3K27me3. We also find that developmental enhancers exhibit components of this signature, including hypersensitivity, H3K27ac enrichment and H3K27me3 depletion, at lower levels in tissues in which they are not active. Our results establish histone modification profiling as a tool for developmental enhancer discovery, and suggest that enhancers maintain an open chromatin state in multiple embryonic tissues independent of their activity level. Examination of genome wide H3K27ac and H3K27me3 histone modifications and gene expression in early mouse embryonic limb tissue.

2012-03-16 | E-GEOD-30641 | biostudies-arrayexpress

Multi-Omics Analyses Revealed Conserved Aging Signatures in Mice

Project description:Studies on aging have largely included one or two OMICS layers, which may not necessarily reflect the signatures of other layers. Moreover, most aging studies have often compared very young (4-5 wks) mice with old (24 months) mice which does not reflect the aging transition after the attainment of adulthood. Therefore, we aimed to study and compared muti-OMICS aging signatures across key metabolic tissues of mature adults (6 months) and old (24 months) C57BL/6J mice (the most commonly used mouse strain). Here we compared the differentially regulated genes and enriched pathways for transcriptome, proteome and epigenome (H3K27ac, H3K4me3, H3K27me3, DNA methylation) across liver, heart, and quadriceps muscle. The major aging associated pathways cross multiple layers and tissues are decreased RNA metabolism, transcription, and translation at transcript and protein levels however increased potential of transcription at DNA methylation and H3K27ac levels.

2021-11-30 | PXD011142 | Pride

Comprehensive Epigenetic Landscape of Rheumatoid Arthritis Fibroblast-like Synoviocytes [WGBS]

Project description:Epigenetics is important in the pathogenesis of immune-mediated diseases like rheumatoid arthritis (RA). Here we show the first complete epigenomic characterization of RA fibroblast-like synoviocytes (FLS) by profiling histone modifications (H3K27ac, H3K4me1, H3K4me3, H3K36me3, H3K27me3, H3K9me3), open chromatin, RNA expression and whole genome DNA methylation. To address the complex multidimensional relationship and reveal the epigenetic regulation of RA, we perform integrative analyses using a novel unbiased method to identify genomic regions with similar profiles. Epigenomically similar regions exist in RA cells are particularly associated with active enhancers and promoters as well as specific transcription factor binding motifs. Differentially marked genes are enriched for immunological and unexpected pathways, with “Huntington's Disease Signaling” identified as particularly prominent. We validate the relevance of this pathway to RA by showing that Huntingtin-interacting protein-1 regulates FLS invasion into matrix. This work establishes a high-resolution epigenomic landscape of RA and demonstrates the potential for integrative analyses to identify unanticipated therapeutic targets.

2018-04-30 | GSE112657 | GEO

Comprehensive Epigenetic Landscape of Rheumatoid Arthritis Fibroblast-like Synoviocytes [ChIP-seq]

2018-04-30 | GSE112655 | GEO

Comprehensive Epigenetic Landscape of Rheumatoid Arthritis Fibroblast-like Synoviocytes [ATAC-seq]

2018-04-30 | GSE112654 | GEO

Comprehensive Epigenetic Landscape of Rheumatoid Arthritis Fibroblast-like Synoviocytes [RNA-seq]

2018-04-30 | GSE112656 | GEO