The RNA binding proteins ZFP36L1 and ZFP36L2 modulate transcriptional and post-transcriptional genome wide effects of glucocorticoids
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE213495 | GEO | 2023/11/21
REPOSITORIES: GEO
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Project description:We conducted RNA/RNA binding protein immunoprecipitation (RIP) followed by high throughput sequencing to identify mRNA targets of Brf1 (Zfp36l1) and Brf2 (Zfp36l2) in mouse embryonic stem cells. We collected over 190 million sequencing reads and identified many highly enriched protein coding mRNAs. Gene ontology analysis of enriched genes reveals that transcription factors and intercellular signaling proteins account for a large fraction of the targets, many of which are important for pluripotency and differentiation. Identification of Brf1 and Brf2 mRNA targets
2014-04-30 | E-GEOD-40104 | biostudies-arrayexpress
Project description:Purpose: Conditional knockout of Zfp36l1 Zfp36l2 early in lymphocyte development leads to a bypass of beta-selection and subsequently T cell acute lymphoblastic leukemia. This RNA seq experiment aimed to determine the molecular pathways affected by loss of Zfp36l1 and Zfp36l2, and to deduce direct targets of these RNA binding proteins. Methods: RNA was isolated from sorted Zfp36l1fl/fl; Zfp36l2fl/fl DN3a (Lineage-negative, CD44-, Kitlow, CD25+, CD98low) and DN3b (Lineage-negative, CD44-, Kitlow, CD25intermediate, CD98+) cells as well as Zfp36l1fl/fl; Zfp36l2fl/fl; CD2cre DN3 (Lineage-negative, CD44-, Kitlow, CD25+) cells with the RNeasy Micro Kit (Qiagen). RNAseq libraries were prepared from 20-200ng RNA using the TruSeq Stranded Total RNA and rRNA Removal Mix â?? Gold from Illumina. Libraries were sequenced by Hiseq in 100bp single-end reads. The reads were trimmed to remove adapter sequences using Trim Galore then mapped using Tophat (version 2.0.12) to the GRCm38 mouse assembly; reads with an identical sequence to more than one genomic locus were not mapped. Quality control analysis was carried out with FastQC. Reads were counted using htseq-count tool and mouse gtf file version 78. Results: Differences in the abundance of transcripts between DCKO and control samples were calculated in the R/Bioconductor program DESeq2 (version 1.6.3). Adjusted P values for differential expression were calculated in DESeq2 using a Benjamini-Hochberg correction: genes with an adjusted p-value of less than 5% were considered significant. Differentially expressed mouse transcripts identified using DESeq2 were analyzed for gene set enrichment using Toppfun. Conclusions: We identified an enrichment of mRNAs involved in cell cycle progression within Zfp36l1 Zfp36l2 double conditional knockouts. 4 biological replicates of control DN3a, control DN3b and DCKO DN3-like cells were analyzed
2016-09-05 | E-GEOD-79174 | biostudies-arrayexpress
Project description:We report our study of the function of two members of the TTP (tristetraprolin) mRNA binding protein family, Zfp36l1 and Zfp36l2, in retinal development. We found that Zfp36l1 and Zfp36l2 were expressed in retinal progenitor cells during development and Müller glial cells and photoreceptors in the mature retina. Our analysis of the mutant retinas showed that, whereas the single knockout retinas appeared largely normal, the double knockout (DKO) retina manifested decreased RPC proliferation and increased differentiation of multiple retinal cell types. RNA-seq analysis not only confirmed the imbalance of proliferation and differentiation in the DKO retina but also revealed Zfp36l1 and Zfp36l2 interact with multiple signaling pathways including the sonic hedgehog pathway and the Notch pathway, to regulate this process.
2021-09-01 | GSE158718 | GEO
Project description:We conducted RNA/RNA binding protein immunoprecipitation (RIP) followed by high throughput sequencing to identify mRNA targets of Brf1 (Zfp36l1) and Brf2 (Zfp36l2) in mouse embryonic stem cells. We collected over 190 million sequencing reads and identified many highly enriched protein coding mRNAs. Gene ontology analysis of enriched genes reveals that transcription factors and intercellular signaling proteins account for a large fraction of the targets, many of which are important for pluripotency and differentiation.
2014-04-30 | GSE40104 | GEO
Project description:Purpose: Conditional knockout of Zfp36l1 Zfp36l2 in pro-B cells perturbs B cell development leading to reduced V(D)J recombination and diminished numbers of cells in successive stages of development. This RNA seq experiment aimed to determine the molecular pathways affected by loss of Zfp36l1 and Zfp36l2, and to deduce direct targets of these RNA binding proteins. Methods: RNAseq libraries were prepared from 0.1 µg of RNA from sorted control and DCKO late pre-B cells using TruSeq RNA sample preparation kit v2 modified to be strand specific using the dUTP method. Libraries were sequenced by an Illumina genome analyzer II measuring 54bp single-end reads. Over 30 million reads were measured from each sample. The reads were trimmed to remove adapter sequences using Trim Galore then mapped using Tophat (version 1.1.4) to the NCBIm37 mouse assembly (April 2007, strain C57BL/6J); reads with an identical sequence to more than one genomic locus were not mapped. Quality control analysis was carried out with FastQC. Results: Read counts for each gene were generated in SeqMonk: transcripts from the same gene were collapsed into a single transcript containing all exons, so total reads were counted without considering alternative splice forms. Since the libraries were strand-specific only reads on the opposing strand were counted. Differences in the abundance of transcripts between DCKO and control late pre-B cells were calculated in the R/Bioconductor program DESeq (version 1.12.1). Adjusted P values for differential expression were calculated in DESeq using a Benjamini-Hochberg correction: genes with an adjusted p-value of less than 5% were considered significant. Differentially expressed mouse transcripts identified using DESeq were analyzed for gene set enrichment using Toppfun. Conclusions: We identified an enrichment of mRNAs involved in cell cycle progression within Zfp36l1 Zfp36l2 double conditional knockouts.
2016-04-21 | GSE78240 | GEO
Project description:Purpose: Conditional knockout of Zfp36l1 Zfp36l2 early in lymphocyte development leads to a bypass of beta-selection and subsequently T cell acute lymphoblastic leukemia. This RNA seq experiment aimed to determine the molecular pathways affected by loss of Zfp36l1 and Zfp36l2, and to deduce direct targets of these RNA binding proteins. Methods: RNA was isolated from sorted Zfp36l1fl/fl; Zfp36l2fl/fl DN3a (Lineage-negative, CD44-, Kitlow, CD25+, CD98low) and DN3b (Lineage-negative, CD44-, Kitlow, CD25intermediate, CD98+) cells as well as Zfp36l1fl/fl; Zfp36l2fl/fl; CD2cre DN3 (Lineage-negative, CD44-, Kitlow, CD25+) cells with the RNeasy Micro Kit (Qiagen). RNAseq libraries were prepared from 20-200ng RNA using the TruSeq Stranded Total RNA and rRNA Removal Mix – Gold from Illumina. Libraries were sequenced by Hiseq in 100bp single-end reads. The reads were trimmed to remove adapter sequences using Trim Galore then mapped using Tophat (version 2.0.12) to the GRCm38 mouse assembly; reads with an identical sequence to more than one genomic locus were not mapped. Quality control analysis was carried out with FastQC. Reads were counted using htseq-count tool and mouse gtf file version 78. Results: Differences in the abundance of transcripts between DCKO and control samples were calculated in the R/Bioconductor program DESeq2 (version 1.6.3). Adjusted P values for differential expression were calculated in DESeq2 using a Benjamini-Hochberg correction: genes with an adjusted p-value of less than 5% were considered significant. Differentially expressed mouse transcripts identified using DESeq2 were analyzed for gene set enrichment using Toppfun. Conclusions: We identified an enrichment of mRNAs involved in cell cycle progression within Zfp36l1 Zfp36l2 double conditional knockouts.
2016-09-05 | GSE79174 | GEO
Project description:Late pre-B cell tranLate pre-B cell transcriptomes from Zfp36l1 Zfp36l2 double knockout micescriptomes from Zfp36l1 Zfp36l2 double knockout mice
| PRJNA313054 | ENA
Project description:Purpose: We aimed to identify the targets of the RNA binding protein ZFP36L1 in thymoctes. Methods: Total naïve thymocytes from control or DCKO mice were treated with UV light to crosslink RNA and proteins, then RNA-protein complexes were pulled down with anti-ZFP36L1. RNA was extracted and used to make cDNS libraries that were then sequenced by MiSeq 150bp single-end read (Sample 1) and HiSeq2500 RapidRun 50bp single-end read (sample 2, 3). Results: Sample demultiplexing was performed by identification of the 3 known bases of the 7 bases barcode introduced in the 5â end of the read by the RCLIP primer. The remaining four random bases were used to remove PCR duplicate reads. Reads were trimmed to remove any adaptor sequence and barcodes before mapping reads to genome GRCm38 using Bowtie. After read mapping, the single-nucleotide at position -1 was annotated as unique ZFP36L1 crosslink site. Identification of highly significant ZFP36L1 binding sites was performed using iCount to assign a FDR to each crosslink site. Conclusions: We identified ZFP36L1 binding sites in 8675 thymocyte mRNAs. Individual nucleotide resolution cross linking immunoprecipitation (iCLIP) of ZFP36L1-bound RNAs in total naive thymocytes from C57BL/6 mice.
2016-09-05 | E-GEOD-79178 | biostudies-arrayexpress
Project description:The zinc finger protein 36-like 2, ZFP36L2, is a member of a small family of RNA-binding proteins composed by ZFP36 (also known as tristetraprolin, TTP), ZFP36L1 and ZFP36L2 in humans, with corresponding murine orthologs. These proteins bind to adenine uridine-rich element (ARE) in the 3’untranslated region of target messenger RNA and stimulate target degradation. ZFP36 functions as an anti-inflammatory modulator in murine models of inflammatory diseases by down-regulating the production of inflammatory cytokines such as tumor necrosis factor-alpha. However, how ZFP36L1 and ZFP36L2 alter the function of CD4+ T cells is not completely understood. We addressed this issue by searching for the target genes of ZFP36L2 by comprehensive transcriptome analysis. We observed that ZFP36L2 is highly expressed in naïve CD4+ T cells; however, when CD4+ T cells are stimulated with T cell receptors, ZFP36L2 expression is rapidly reduced in both humans and mice. Among CD4+ T cell populations, the expression levels of ZFP36L2 in regulatory T cells (Tregs) were lower than those in naïve or effector CD4+ T cells. RNA-sequence analysis revealed that the forced expression of ZFP36L2 decreased Ikzf2 (encoding Helios) expression in Foxp3+ Tregs and inhibited the ability of induced Tregs (iTregs). ZFP36L2 destabilized the 3’untranslated region of Ikzf2 mRNA, which contains AU-rich elements. These results indicate that ZFP36L2 reduces the expression of Ikzf2 and suppresses iTreg function, suggesting that the inhibition of ZFP36L2 in iTregs could be a therapeutic strategy for autoimmune diseases.
2020-05-21 | GSE150937 | GEO
Project description:Genome-wide ZFP36L2 binding on RNA in AML cells
2021-01-19 | GSE146516 | GEO