Identification of Lef1-dependent genes in zebrafish and mouse hypothalamus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: GSE98519
PROVIDER: PRJNA385330 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5504150.fastq.gz | Fastqsanger.gz | |||
| SRR5504160.fastq.gz | Fastqsanger.gz | |||
| SRR5504151.fastq.gz | Fastqsanger.gz | |||
| SRR5504161.fastq.gz | Fastqsanger.gz | |||
| SRR5504152.fastq.gz | Fastqsanger.gz |
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Project description:Recently global gene expression profiling of patients samples lead to a molecular definition of Burkitt Lymphoma (BL) with lymphocyte enhancer-binding factor 1 (LEF1) as a signature gene. Here we report the discovery of nucleic LEF1 in a very high proportion of BL cases (15/18) and LEF1 target genes. Germinal center B cells were devoid of detectable nuclear LEF1 expression as mantle cell lymphoma (0/5), marginal zone lymphoma (0/6), follicular lymphoma (0/12) or diffuse large B cell lymphoma (DLBCL) (1/31). Using whole genome gene expression profiling after transient knockdown of LEF1 in BL cell lines, new LEF1 target genes were identified. The joint expression of these genes in primary BL samples shows that LEF1 is not only expressed aberrantly in BL but also transcriptionally active. Our study identified aberrantly expressed LEF1 and its target genes suggesting an important functional role in BLs.
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Project description:Quantitative and qualitative changes in mRNA translation occur in tumor cells and support cancer progression and metastasis. Post-transcriptional nucleoside modifications of transfer RNAs (tRNAs) at the wobble U34 base are highly conserved and contribute to translation fidelity. Here, we show that ELP3 and CTU1/2, partner enzymes in U34 mcm5s2-tRNA modification, are upregulated in human breast cancers and sustain metastasis. Elp3 genetic ablation strongly impaired invasion and metastasis formation in the PyMT model of invasive breast cancer. Mechanistically, ELP3 and CTU1/2 support cellular invasion through the translation of the oncoprotein DEK. As a result, DEK promotes the IRES-dependent translation of the pro-invasive transcription factor LEF1. Consistently, a DEK mutant, whose codon composition is independent of U34 mcm5s2-tRNA modification, escapes the ELP3- and CTU1-dependent regulation and restores the IRES-dependent LEF1 expression. Our results demonstrate the key role of U34 tRNA modification to support specific translation during breast cancer progression and highlight a functional link between tRNA modification- and IRES-dependent translation during tumor cell invasion and metastasis.analysis of transcriptomic changes due to Elp3genetic deletion in cells extracted from PyMT mammary tumors.
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Project description:Our previous study suggested persistent transgenerational effects of fluoxetine (FLX) exposure, in both environmental and therapeutic concentrations, on stress response and behaviour up to 3 generation withdrawn from exposure in larvae and adult zebrafish. To lay the foundations of the mechanistic of such transgenerational effects, we studied the effect of FLX on stress response in brain tissues (telencephalon and hypothalamus) of larvae and adult zebrafish using differentially expressed genes at the transcriptome level. To monitor the stress response, we used a transgenic zebrafish line (SR4G) which are expressing green fluorescence protein (GFP) in response to endogenous and exogenous glucocorticoids. The transcriptome analysis of GFP RNA as an internal control, provided us with an invaluable tool to clearly visualize and differentiate between stressed and unstressed groups as per treatments. To stimulate stress in both larvae and adult zebrafish we used a modified net stressing technique consisting of consecutive sequence of air exposure and incubation intervals. A pool of 22 larvae heads and a pool of 5 telencephalon and 5 hypothalamus dissected tissues were used as the target tissues for RNA extraction. All experiments were replicated in n=6 per 4 different groups including Control-Unstressed (Cnt-U), Control-Stressed (Cnt-S), Fluoxetine-Unstressed (FLX-U), and Fluoxetine-Stressed (FLX-S) using pools of larvae heads, telencephalon, and hypothalamus. After total RNA extraction, using Illumina technology all samples were sequence and the list of differentially expressed genes (DEGs) were produced using DSEQ pipeline in R.
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