Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The tissue-specific lncRNA Fendrr is an essential regulator of heart and body wall development in the mouse

ABSTRACT: The histone modifying complexes PRC2 and TrxG/MLL play pivotal roles in determining the activation state of genes controlling pluripotency, lineage commitment, and cell differentiation. Long non-coding RNAs (lncRNAs) can bind to either complex, and some have been shown to act as modulators of PRC2 or TrxG/MLL activity. Here we show that the lateral mesoderm-specific lncRNA Fendrr is essential for proper heart and body wall development in the mouse. Embryos lacking Fendrr displayed upregulation of several transcription factors controlling lateral plate or cardiac mesoderm differentiation, accompanied by a drastic reduction in PRC2 occupancy along with decreased H3K27 trimethylation and/or an increase in H3K4 trimethylation at their promoters. Fendrr binds to both the PRC2 and TrxG/MLL complexes, suggesting that it acts as modulator of chromatin signatures that define gene activity. Thus, our work identifies a lncRNA that plays an essential role in fine-tuning the regulatory networks which control the fate of lateral mesoderm derivatives.

ORGANISM(S): Mus musculus

PROVIDER: GSE43078 | GEO | 2013/01/28

SECONDARY ACCESSION(S): PRJNA184736

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

The tissue-specific lncRNA Fendrr is an essential regulator of heart and body wall development in the mouse

Project description:The histone modifying complexes PRC2 and TrxG/MLL play pivotal roles in determining the activation state of genes controlling pluripotency, lineage commitment, and cell differentiation. Long non-coding RNAs (lncRNAs) can bind to either complex, and some have been shown to act as modulators of PRC2 or TrxG/MLL activity. Here we show that the lateral mesoderm-specific lncRNA Fendrr is essential for proper heart and body wall development in the mouse. Embryos lacking Fendrr displayed upregulation of several transcription factors controlling lateral plate or cardiac mesoderm differentiation, accompanied by a drastic reduction in PRC2 occupancy along with decreased H3K27 trimethylation and/or an increase in H3K4 trimethylation at their promoters. Fendrr binds to both the PRC2 and TrxG/MLL complexes, suggesting that it acts as modulator of chromatin signatures that define gene activity. Thus, our work identifies a lncRNA that plays an essential role in fine-tuning the regulatory networks which control the fate of lateral mesoderm derivatives. The transcriptomes of ventricles isolated from wildtype (WT) and Fendrr knock-out (KO) E12.5 embryos, obtained from tratraploid complementations of embryonic stem cells, were analyzed by strand-specific RNA-Seq of ribosomal RNA-depleted, total RNA.

2013-01-28 | E-GEOD-43078 | biostudies-arrayexpress

The LncRNA Fendrr Regulates Lung Development via its Triplex Forming Site the Expression of Fibrosis Genes

Project description:Long non-coding RNAs are a very versatile class of molecules that have important roles in regulating a cells function, including regulating other genes on the transcriptional level. One of these mechanisms is that RNA can directly interact with DNA by recruiting additional components such as proteins to these sites via a RNA:dsDNA triplex formation. We genetically deleted the triplex forming sequence from the lncRNA Fendrr in mice and find that this FendrrBox is partially required for Fendrr function. we We find that the loss of the triplex forming site in developing lungs causes a dysregulation of gene programs, associated with lung fibrosis. Deregulated genes that contain a FendrrBox binding element in their promoter are regulated by Wnt signaling, together with Fendrr, implicating that Fendrr acts in concert with Wnt signaling to regulate lung fibrosis.

2023-04-30 | GSE186703 | GEO

Human lung cancer Cells: Control vs. FENDRR stably over-expressed lung cancer cells

Project description:Transcriptional profiling of human lung cancer cell lines A549 comparing control cells transfected with an empty lentiviral expression vector pEZ-Lv201 and A549 cells transfected with a pEZ-Lv201-FENDRR. The latter forms a FENDRR stably over-expressed cell lines. Goal was to to assess the alteration of gene expression profiles caused by FENDRR upregulation.

2016-11-15 | GSE89828 | GEO

PRC2 is required for acute myeloid leukemias initiated by MLL-AF9

Project description:The transcriptional activating and repressive functions performed by Trithorax and Polycomb group complexes, respectively, are critical for to maintain cellular fates in ontogeny and in cancer. Here we report that leukemias initiated by a Trithorax-related oncogene, MLL-AF9, depend upon the Polycomb Repressive Complex 2 (PRC2) to sustain a transformed cellular state. RNAi mediated suppression of PRC2 subunits is sufficient to inhibit proliferation of MLL-AF9 leukemias, with little impact on growth of non-transformed cells. This requirement is partly due to PRC2-mediated transcriptional repression of several anti-self-renewal regulators, including Cdkn2a. These results suggest that, unlike the classical antagonism generally observed between Polycomb and Trithorax group proteins during development, the activities of these two pathways can cooperate to promote myeloid neoplasia. In order to understand downstream targets of PRC2 complex in MLL-AF9 leukemia, we performed array in murine MLL-AF9/NrasG12D cell line under the condition that two subunits of PRC2(Eed and Suz12) were suppressed by using shRNAs.

2013-07-01 | E-GEOD-34183 | biostudies-arrayexpress

Effect of FENDRR on genetic expressions of primary liver cancer based on next generation sequencing

Project description:Primary liver cancer (PLC) is the third largest contributor to cancer mortality in the world. PLC is a heterogeneous disease that encompasses several biologically distinct subtypes including hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular-cholangiocarcinoma (CHC). The cells were cultured in DMEM medium supplemented with 10% fetal bovine serum and 1% antibiotic-antimitotic solution. The HCC cell line LM3 and ICCA cell line RBE were transfected using Lipofectamine 3000 reagent following the manufacturer’s protocol and incubated for 48h for further analysis. The gene expression profiles were analyzed of LM3 and RBE cells transfected with si-FENDRR or si-NC to assess effect of FENDRR on genetic expressions of PLC.

2021-03-15 | GSE168885 | GEO

Long noncoding RNA FENDRR inhibits lung fibroblast proliferation via a reduction of beta-catenin

Project description:Adenovirus-mediated FENDRR transfer to the lungs of mice reduced asbestos-induced fibrotic lesions and collagen deposition.RNA sequencing analysis was used to profile the gene expression in the lungs of asbestos-treated (VC-Cro) mice compared to control (VC-TiO2).

2021-05-26 | GSE175496 | GEO

Chromatin interaction profiles at bivalent genes by multiplexed splinkerette 4C sequencing

Project description:To examine chromatin interaction profiles around bivalent gene loci, we developed a multiplexed splinkerette Chromosome Conformation Capture Combined with high-throughput sequencing (ms4C-seq). By using ms4C-seq, we showed that bivalent gene loci tend to be colocalized in hiPSCs and that the colocalization requires PRC1, PRC2 and TrxG complexes that are the essential regulatory factors for maintenance of developmental genes in the transcriptionally poised state.

2017-11-04 | GSE90782 | GEO

Genome-wide profiling of long non-coding RNAs in Arabidopsis

Project description:We developed a stringent selection pipeline for lncRNA identification, combining high-throughput RNA sequencing and computational approaches. Using this pipeline, we annotated 1,353 lncRNAs in Arabidopsis thaliana. We further found that one fifth of the lncRNAs were associated with Polycomb repressive complex 2 (PRC2). Some PRC2-associated lncRNAs could repress the transcription of their neighboring genes through mediating histone H3 lysine 27 trimethylation.

2015-11-28 | GSE42695 | GEO

Two distinct functional axes of positive feedback-enforced PRC2 recruitment in mouse embryonic stem cells

Project description:Polycomb Repressive Complex 2 (PRC2) plays an essential role in development by catalysing trimethylation of histone H3 lysine 27 (H3K27me3), resulting in gene repression. PRC2 consists of two sub-complexes, PRC2.1 and PRC2.2, in which the PRC2 core associates with distinct ancillary subunits such as MTF2 and JARID2, respectively. Both MTF2, present in PRC2.1, and JARID2, present in PRC2.2, play a role in core PRC2 recruitment to target genes in mouse embryonic stem cells (mESCs). However, it remains unclear how these distinct sub-complexes cooperate to establish H3K27me3 domains. Here, we combine a range of Polycomb mutant mESCs with chemical inhibition of PRC2 catalytic activity, to systematically dissect their relative contributions to PRC2 binding to target loci. We find that PRC2.1 and PRC2.2 mediate two distinct paths for recruitment, with mutually reinforced binding. Part of the cross-talk between PRC2.1 and PRC2.2 occurs via their catalytic product H3K27me3, which is bound by the PRC2 core-subunit EED, thereby mediating a positive feedback. Strikingly, removal of either JARID2 or H3K27me3 only has a minor effect on PRC2 recruitment, whereas their combined ablation largely attenuates PRC2 recruitment. This strongly suggests an unexpected redundancy between JARID2 and EED-H3K27me3-mediated recruitment of PRC2. Furthermore, we demonstrate that all core PRC2 recruitment occurs through the combined action of MTF2-mediated recruitment of PRC2.1 to DNA and PRC1-mediated recruitment of JARID2-containing PRC2.2. Both axes of binding are supported by EED-H3K27me3 positive feedback, but to a different degree. Finally, we provide evidence that PRC1 and PRC2 mutually reinforce reciprocal binding. Together, these data disentangle the interdependent and cooperative interactions between Polycomb complexes that are important to establish Polycomb repression at target sites.

2020-08-07 | PXD014290 | Pride

Two distinct functional axes of positive feedback-enforced PRC2 recruitment in mouse embryonic stem cells

2021-09-22 | PXD020684 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data