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Tet-dependent 5-hydroxymethyl-Cytosine modification of mRNA regulates the axon guidance genes robo2 and slit in Drosophila [ChIP Embryo]

ABSTRACT: Tet-dependent 5-hydroxymethyl-Cytosine modification of mRNA regulates the axon guidance genes robo2 and slit in Drosophila [ChIP Embryo]

PROVIDER: PRJNA938121 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23602555.fastq.gz	Fastqsanger.gz
	SRR23602556.fastq.gz	Fastqsanger.gz
	SRR23602557.fastq.gz	Fastqsanger.gz
	SRR23602558.fastq.gz	Fastqsanger.gz

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Similar Datasets

Tet-dependent 5-hydroxymethyl-Cytosine modification of mRNA regulates the axon guidance genes robo2 and slit in Drosophila [hMeRIP]

Project description:Modifications of mRNA, especially methylation of adenosine, have recently drawn much attention. The much rarer modification, 5-hydroxymethylation of cytosine (5hmC), is not well understood and is the subject of this study. Vertebrate Tet proteins are 5-methylcytosine (5mC) hydroxylases enzymes catalyzing the transition of 5mC to 5hmC in DNA and have recently been shown to have the same function in messenger RNAs in both vertebrates and in Drosophila. The Tet gene is essential in Drosophila because Tet knock-out animals do not reach adulthood. We describe the identification of Tet-target genes in the embryo and larval brain by determining Tet DNA-binding sites throughout the genome and by mapping the Tet-dependent 5hmrC modifications transcriptome-wide. 5hmrC-modified sites can be found along the entire transcript and are preferentially located at the promoter where they overlap with histone H3K4me3 peaks. The identified mRNAs are frequently involved in neuron and axon development and Tet knock-out led to a reduction of 5hmrC marks on specific mRNAs. Among the Tet-target genes were the robo2 receptor and its slit ligand that function in axon guidance in Drosophila and in vertebrates. Tet knock-out embryos show overlapping phenotypes with robo2 and are sensitized to reduced levels of slit. Both Robo2 and Slit protein levels were markedly reduced in Tet KO larval brains. Our results establish a role for Tet-dependent 5hmrC in facilitating the translation of modified mRNAs, primarily in developing nerve cells.

2024-02-23 | GSE225979 | GEO

Tet-dependent 5-hydroxymethyl-Cytosine modification of mRNA regulates the axon guidance genes robo2 and slit in Drosophila [ChIP LBF]

2024-02-23 | GSE225970 | GEO

Tet-dependent 5-hydroxymethyl-Cytosine modification of mRNA regulates the axon guidance genes robo2 and slit in Drosophila [ChIP Embryo]

2024-02-23 | GSE225969 | GEO

Tet-dependent 5-hydroxymethyl-Cytosine modification of mRNA regulates the axon guidance genes robo2 and slit in Drosophila [hMeRIP]

Project description:Tet-dependent 5-hydroxymethyl-Cytosine modification of mRNA regulates the axon guidance genes robo2 and slit in Drosophila [hMeRIP]

| PRJNA938138 | ENA

Tet-dependent 5-hydroxymethyl-Cytosine modification of mRNA regulates the axon guidance genes robo2 and slit in Drosophila [ChIP LBF]

Project description:Tet-dependent 5-hydroxymethyl-Cytosine modification of mRNA regulates the axon guidance genes robo2 and slit in Drosophila [ChIP LBF]

| PRJNA938124 | ENA

Tet-dependent 5-hydroxymethyl-Cytosine modification of mRNA regulates the axon guidance genes robo2 and slit in Drosophila.

| S-EPMC9949232 | biostudies-literature

Tet-dependent 5-hydroxymethyl-Cytosine modification of mRNA regulates axon guidance genes in Drosophila

Project description:Tet-dependent 5-hydroxymethyl-Cytosine modification of mRNA regulates axon guidance genes in Drosophila

| PRJNA938136 | ENA

Differential Expression Analysis of the SLIT Family in Different Brain Regions

Project description:The ageing human brain undergoes extensive remodelling of its extracellular matrix (ECM), yet the regional specificity and molecular drivers remain poorly defined. Here we combine bulk RNA-sequencing of post-mortem tissue (n = 63 across eight regions) with independent validation in the Genotype-Tissue Expression (GTEx) cohort (n = 962) to chart the expression landscape of the 239-member core matrisome. Hippocampus emerged as a major ECM outlier, with 114 matrisome genes—dominated by glycoproteins—up-regulated compared to the other seven regions (Fisher’s combined test, FDR < 0.05). Genes coding the axon-guidance ligands SLIT1, SLIT2 and SLIT3 ranked among the top hippocampal signatures and displayed strong co-expression with ROBO2 (r > 0.70). Age-stratified analysis in GTEx revealed a concerted decline of the SLIT-ROBO2 axis after 60y, aligning with hallmarks of cognitive ageing. Immunohistochemistry and western blotting (n = 3 per region) supported regional and subcellular patterns of SLITs ROBO2. These findings identify the SLIT-ROBO2 module as a hippocampus-centric, age-labile component of the human matrisome. We propose that sustained SLIT-ROBO signalling supports hippocampal synaptic plasticity, whereas its late-life attenuation may diminish structural resilience and heighten vulnerability to neurodegeneration. Our resource provides a framework for targeting ECM pathways to preserve brain connectivity during ageing.

2026-03-01 | GSE311762 | GEO

Axon Guidance Receptor ROBO3 Modulates Subtype Identity and Prognosis via AXL-associated Inflammatory Network in Pancreatic Cancer

Project description:Recently, genome-wide molecular analyses have identified an altered axon guidance SLIT-ROBO signaling pathway in Pancreatic ductal adenocarcinoma (PDAC). To examine whether ROBO3 signaling is involved in the transcriptional determination of basal-like PDAC-subtype specification and functions, we performed RNA-seq analysis following ROBO3 silencing in the basal-like cell line PANC1.

2022-07-31 | E-MTAB-11476 | biostudies-arrayexpress

The Slit-binding Ig1 domain is required for multiple axon guidance activities of Drosophila Robo2.

Project description:Drosophila Robo2 is a member of the evolutionarily conserved Roundabout (Robo) family of axon guidance receptors. Robo receptors signal midline repulsion in response to Slit ligands, which bind to the N-terminal Ig1 domain in most family members. In the Drosophila embryonic ventral nerve cord, Robo1 and Robo2 signal Slit-dependent midline repulsion, while Robo2 also regulates the medial-lateral position of longitudinal axon pathways and acts non-autonomously to promote midline crossing of commissural axons. While Robo2 signals midline repulsion in response to Slit, it is less clear whether Robo2's other activities are also Slit-dependent. To determine which of Robo2's axon guidance roles depend on its Slit-binding Ig1 domain, we used a clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-based strategy to replace the endogenous robo2 gene with a robo2 variant lacking the Ig1 domain (robo2∆Ig1). We compare the expression and localization of Robo2∆Ig1 protein with full-length Robo2 in embryonic neurons in vivo and examine its ability to substitute for Robo2 to mediate midline repulsion and lateral axon pathway formation. We find that the removal of the Ig1 domain from Robo2∆Ig1 disrupts both of these axon guidance activities. In addition, we find that the Ig1 domain of Robo2 is required for its proper subcellular localization in embryonic neurons, a role that is not shared by the Ig1 domain of Robo1. Finally, we report that although FasII-positive lateral axons are misguided in embryos expressing Robo2∆Ig1, the axons that normally express Robo2 are correctly guided to the lateral zone, suggesting that Robo2 may guide lateral longitudinal axons through a cell non-autonomous mechanism.

| S-EPMC8446337 | biostudies-literature

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