scholarly journals Spi-1 and Fli-1 Directly Activate Common Target Genes Involved in Ribosome Biogenesis in Friend Erythroleukemic Cells

2009 ◽  
Vol 29 (10) ◽  
pp. 2852-2864 ◽  
Author(s):  
Gaëtan Juban ◽  
Guillaume Giraud ◽  
Boris Guyot ◽  
Stéphane Belin ◽  
Jean-Jacques Diaz ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Ribosome Biogenesis ◽  
Target Genes ◽  
Transcriptome Profiling ◽  
Gene Promoters ◽  
Ets Transcription Factors ◽  
Dna Binding Site ◽  
Friend Erythroleukemic Cells ◽  
Interfering Rna ◽  
Erythroleukemic Cells

ABSTRACT Spi-1 and Fli-1 are ETS transcription factors recurrently deregulated in mouse erythroleukemia induced by Friend viruses. Since they share the same core DNA binding site, we investigated whether they may contribute to erythroleukemia by common mechanisms. Using inducible knockdown, we demonstrated that Fli-1 contributes to proliferation, survival, and differentiation arrest of erythroleukemic cells harboring an activated fli-1 locus. Similarly, we used inducible Fli-1 knockdown and either hexamethylenebisacetamide (HMBA)- or small interfering RNA-mediated Spi-1 knockdown to investigate their respective contributions in erythroleukemic cells harboring an activated spi-1 locus. In these cells, simple or double knockdown of both Spi-1 and Fli-1 additively contributed to induce proliferation arrest and differentiation. Transcriptome profiling revealed that virtually all transcripts affected by both Fli-1 knockdown and HMBA are affected in an additive manner. Among these additively downregulated transcripts, more than 20% encode proteins involved in ribosome biogenesis, and conserved ETS binding sites are present in their gene promoters. Through chromatin immunoprecipitation, we demonstrated the association of Spi-1 and Fli-1 on these promoters in Friend erythroleukemic cells. These data lead us to propose that the oncogenicity of Spi-1, Fli-1, and possibly other ETS transcription factors may involve their ability to stimulate ribosome biogenesis.

scholarly journals The PARP Inhibitor Olaparib Modulates the Transcriptional Regulatory Networks of Long Non-Coding RNAs during Vasculogenic Mimicry

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2690
Author(s):  
Mónica Fernández-Cortés ◽  
Eduardo Andrés-León ◽  
Francisco Javier Oliver
Keyword(s):  
Transcription Factors ◽  
Binding Sites ◽  
Regulatory Networks ◽  
Target Genes ◽  
Parp Inhibitor ◽  
Vasculogenic Mimicry ◽  
Transcriptome Profiling ◽  
Key Species ◽  
Non Coding Rnas ◽  
The Impact

In highly metastatic tumors, vasculogenic mimicry (VM) involves the acquisition by tumor cells of endothelial-like traits. Poly-(ADP-ribose) polymerase (PARP) inhibitors are currently used against tumors displaying BRCA1/2-dependent deficient homologous recombination, and they may have antimetastatic activity. Long non-coding RNAs (lncRNAs) are emerging as key species-specific regulators of cellular and disease processes. To evaluate the impact of olaparib treatment in the context of non-coding RNA, we have analyzed the expression of lncRNA after performing unbiased whole-transcriptome profiling of human uveal melanoma cells cultured to form VM. RNAseq revealed that the non-coding transcriptomic landscape differed between olaparib-treated and non-treated cells: olaparib significantly modulated the expression of 20 lncRNAs, 11 lncRNAs being upregulated, and 9 downregulated. We subjected the data to different bioinformatics tools and analysis in public databases. We found that copy-number variation alterations in some olaparib-modulated lncRNAs had a statistically significant correlation with alterations in some key tumor suppressor genes. Furthermore, the lncRNAs that were modulated by olaparib appeared to be regulated by common transcription factors: ETS1 had high-score binding sites in the promoters of all olaparib upregulated lncRNAs, while MZF1, RHOXF1 and NR2C2 had high-score binding sites in the promoters of all olaparib downregulated lncRNAs. Finally, we predicted that olaparib-modulated lncRNAs could further regulate several transcription factors and their subsequent target genes in melanoma, suggesting that olaparib may trigger a major shift in gene expression mediated by the regulation lncRNA. Globally, olaparib changed the lncRNA expression landscape during VM affecting angiogenesis-related genes.

scholarly journals Potential Downstream Target Genes of Aberrant ETS Transcription Factors Are Differentially Affected in Ewing’s Sarcoma and Prostate Carcinoma

PLoS ONE ◽  
2012 ◽  
Vol 7 (11) ◽  
pp. e49819 ◽  
Author(s):  
Maria J. Camões ◽  
Paula Paulo ◽  
Franclim R. Ribeiro ◽  
João D. Barros-Silva ◽  
Mafalda Almeida ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Prostate Carcinoma ◽  
Target Genes ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Ets Transcription Factors ◽  
Downstream Target

scholarly journals Eos, MITF, and PU.1 Recruit Corepressors to Osteoclast-Specific Genes in Committed Myeloid Progenitors

2007 ◽  
Vol 27 (11) ◽  
pp. 4018-4027 ◽  
Author(s):  
Rong Hu ◽  
Sudarshana M. Sharma ◽  
Agnieszka Bronisz ◽  
Ruchika Srinivasan ◽  
Uma Sankar ◽  
...  
Keyword(s):  
Target Genes ◽  
Zinc Finger Protein ◽  
Osteoclast Differentiation ◽  
Direct Interaction ◽  
Cathepsin K ◽  
Gene Promoters ◽  
Basal Expression ◽  
Rna Knockdown ◽  
Interfering Rna ◽  
Myeloid Progenitors

ABSTRACT Transcription factors MITF and PU.1 collaborate to increase expression of target genes like cathepsin K (Ctsk) and acid phosphatase 5 (Acp5) during osteoclast differentiation. We show that these factors can also repress transcription of target genes in committed myeloid precursors capable of forming either macrophages or osteoclasts. The direct interaction of MITF and PU.1 with the zinc finger protein Eos, an Ikaros family member, was necessary for repression of Ctsk and Acp5. Eos formed a complex with MITF and PU.1 at target gene promoters and suppressed transcription through recruitment of corepressors CtBP (C-terminal binding protein) and Sin3A, but during osteoclast differentiation, Eos association with Ctsk and Acp5 promoters was significantly decreased. Subsequently, MITF and PU.1 recruited coactivators to these target genes, resulting in robust expression of target genes. Overexpression of Eos in bone marrow-derived precursors disrupted osteoclast differentiation and selectively repressed transcription of MITF/PU.1 targets, while small interfering RNA knockdown of Eos resulted in increased basal expression of Ctsk and Acp5. This work provides a mechanism to account for the modulation of MITF and PU.1 activity in committed myeloid progenitors prior to the initiation of osteoclast differentiation in response to the appropriate extracellular signals.

Regulation of angiogenesis by ETS transcription factors

2009 ◽  
Vol 37 (6) ◽  
pp. 1248-1253 ◽  
Author(s):  
Anna M. Randi ◽  
Andrea Sperone ◽  
Nicola H. Dryden ◽  
Graeme M. Birdsey
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Gene Transcription ◽  
Target Genes ◽  
Ets Transcription Factors ◽  
Ets Family ◽  
Endothelial Gene Expression ◽  
Ets Factors

Transcription factors of the ETS family are important regulators of endothelial gene expression. Here, we review the evidence that ETS factors regulate angiogenesis and briefly discuss the target genes and pathways involved. Finally, we discuss novel evidence that shows how these transcription factors act in a combinatorial fashion with others, through composite sites that may be crucial in determining endothelial specificity in gene transcription.

Control of ribosome biogenesis by oncogenic ETS transcription factors

2008 ◽  
Vol 6 (9) ◽  
pp. 33
Author(s):  
B. Guyot ◽  
G. Juban ◽  
G. Giraud ◽  
J. Textoris ◽  
S. Belin ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Ribosome Biogenesis ◽  
Ets Transcription Factors

scholarly journals Pea3 ETS transcription factors function redundantly to regulate FGF target genes and development in zebrafish

2009 ◽  
Vol 331 (2) ◽  
pp. 518
Author(s):  
Wade Znosko ◽  
Gabriela Molina ◽  
Chengjian Li ◽  
Warren Tsang ◽  
Igor Dawid ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Target Genes ◽  
Ets Transcription Factors

scholarly journals Pattern recognition receptors confer plant salt tolerance via WRKY18/WRKY40 transcription factors

2020 ◽  
Author(s):  
Eliza P. Loo ◽  
Yuri Tajima ◽  
Kohji Yamada ◽  
Taishi Hirase ◽  
Hirotaka Ariga ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Transcription Factors ◽  
Salt Tolerance ◽  
Dna Sequences ◽  
Pathogenic Bacteria ◽  
Target Genes ◽  
Specific Binding ◽  
Transcriptome Profiling ◽  
Pattern Recognition Receptors ◽  
Cross Tolerance

AbstractPattern recognition receptors (PRRs) bind microbe- and damage-associated molecular patterns (MAMPs/DAMPs, respectively) to enhance host immunity in animals and plants. Here, we report that PRRs also confer salt tolerance in the model plant Arabidopsis thaliana following recognition of cognate ligands, such as bacterial flagellin and EF-Tu and the endogenous Pep peptides. Pattern-triggered salt tolerance (PTST) requires the PRR-associated kinases BAK1 and BIK1, and the NADPH oxidase RBOHD. Transcriptome profiling reveals an inventory of PTST target genes, which increase or acquire salt responsiveness following an exposure to immunogenic patterns. In their regulatory DNA sequences, specific binding sites for a subset of WRKY transcription factors are over-represented. Accordingly, PTST requires WRKY40 and WRKY18, which activate salt tolerance-related genes but attenuate pathogen defense-related genes, including the EDS1 immunity activator. PRR signaling leads to sustained WRKY40/WRKY18 accumulation under salt stress and utilizes both WRKYs for salt tolerance. The PRR-WRKY40/WRKY18 module also confers salt tolerance after challenge with non-pathogenic bacteria. Our findings give molecular insight into signaling plasticity underlying biotic-abiotic stress cross-tolerance in plants conferred by PRRs.

Identification of novel genes and pathways regulated by the orphan nuclear receptor COUP-TFII in mouse MA-10 Leydig cells†

2021 ◽  
Author(s):  
Samir Mehanovic ◽  
Raifish E Mendoza-Villarroel ◽  
Karine Mattos ◽  
Philippe Talbot ◽  
Robert S Viger ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Differentially Expressed Genes ◽  
Nuclear Receptor ◽  
Leydig Cells ◽  
Target Genes ◽  
Sex Differentiation ◽  
Gonad Development ◽  
Differentially Expressed ◽  
Gene Promoters ◽  
Orphan Nuclear Receptor

Abstract In males, Leydig cells are the main producers of testosterone and insulin-like 3 (INSL3), two hormones essential for sex differentiation and reproductive functions. Chicken ovalbumin upstream promoter-transcription factors I (COUP-TFI/NR2F1) and COUP-TFII (NR2F2) belong to the steroid/thyroid hormone nuclear receptor superfamily of transcription factors. In the testis, COUP-TFII is expressed and plays a role in the differentiation of cells committed to give rise to fully functional steroidogenic adult Leydig cells. Steroid production has also been shown to be diminished in COUP-TFII-depleted Leydig cells, indicating an important functional role in steroidogenesis. Until now, only a handful of target genes have been identified for COUP-TFII in Leydig cells. To provide new information into the mechanism of action of COUP-TFII in Leydig cells, we performed microarray analyses of COUP-TFII-depleted MA-10 Leydig cells. We identified 262 differentially expressed genes in COUP-TFII-depleted MA-10 cells. Many of the differentially expressed genes are known to be involved in lipid biosynthesis, lipid metabolism, male gonad development, and steroidogenesis. We validated the microarray data for a subset of the modulated genes by RT-qPCR. Downregulated genes included Hsd3b1, Cyp11a1, Prlr, Shp/Nr0b2, Fdx1, Scarb1, Inha and Gsta3. Finally, analysis of the Gsta3 and Inha gene promoters showed that at least two of the downregulated genes are potentially new direct targets for COUP-TFII. These data provide new evidence that further strengthens the important nature of COUP-TFII in steroidogenesis, androgen homeostasis, cellular defense, and differentiation in mouse Leydig cells.

scholarly journals Cancer-specific CTCF binding facilitates oncogenic transcriptional dysregulation

2020 ◽  
Author(s):  
Celestia Fang ◽  
Zhenjia Wang ◽  
Cuijuan Han ◽  
Stephanie L. Safgren ◽  
Kathryn A. Helmin ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Transcription Factors ◽  
Genome Organization ◽  
Target Genes ◽  
Lymphoblastic Leukemia ◽  
Three Dimensional ◽  
Dna Looping ◽  
Ctcf Binding ◽  
Gene Promoters ◽  
Comprehensive Survey

AbstractBackgroundThe three-dimensional genome organization is critical for gene regulation and can malfunction in diseases like cancer. As a key regulator of genome organization, CCCTC-binding factor (CTCF) has been characterized as a DNA-binding protein with important functions in maintaining the topological structure of chromatin and inducing DNA looping. Among the prolific binding sites in the genome, several events with altered CTCF occupancy have been reported as associated with effects in physiology or disease. However, there is no hitherto a comprehensive survey of genome-wide CTCF binding patterns across different human cancers.ResultsTo dissect functions of CTCF binding, we systematically analyze over 700 CTCF ChIP-seq profiles across human tissues and cancers and identify cancer-specific CTCF binding patterns in six cancer types. We show that cancer-specific lost and gained CTCF binding events are associated with altered chromatin interactions in patient samples, but not always with DNA methylation changes or sequence mutations. While lost bindings primarily occur near gene promoters, most gained CTCF binding events are induced by oncogenic transcription factors and exhibit enhancer activities. We validate these findings in T-cell acute lymphoblastic leukemia and show that oncogenic NOTCH1 induces specific CTCF binding and they cooperatively activate expression of target genes, indicating transcriptional condensation phenomena.ConclusionsCancer-specific CTCF binding events are not always associated with DNA methylation changes or mutations, but can be induced by other transcription factors to regulate oncogenic gene expression. Our results substantiate CTCF binding alteration as a functional epigenomic signature of cancer.

Sign in / Sign up

Export Citation Format

Share Document