Similar Datasets
Project description:Glioblastoma multiforme (GBM) is the most common and aggressive malignant brain tumor among adults, which is characterized by high invasion, migration and proliferation abilities. One important process that contributes to the invasiveness of GBM is the epithelial to mesenchymal transition (EMT). EMT is regulated by a set of defined transcription factors which tightly regulate this process, among them is the basic helix-loop-helix family member, TWIST1. Here we show that TWIST1 is methylated on lysine-33 at chromatin by SETD6, a methyltransferase with expression levels correlating with poor survival in GBM patients. RNA-seq analysis in U251 GBM cells suggested that both SETD6 and TWIST1 regulate cell adhesion and migration processes. We further show that TWIST1 methylation attenuates the expression of the long-non-coding RNA, LINC-PINT, thereby suppressing EMT in GBM. Mechanistically, TWIST1 methylation represses the transcription of LINC-PINT by increasing the occupancy of EZH2 and the catalysis of the repressive H3K27me3 mark at the LINC-PINT locus. Under un-methylated conditions, TWIST1 dissociates from the LINC-PINT locus, allowing the expression of LINC-PINT which leads to increased cell adhesion and decreased cell migration. Together, our findings unravel a new mechanistic dimension for selective expression of LINC-PINT mediated by TWIST1 methylation.
2022-08-12 | PXD029361 | Pride
Project description:TWIST1 is known to play a role in the metastatic progression of melanoma. However, the range of TWIST1 targets is poorly charachterized. Here microarray analysis was used to define the TWIST1 regulated transcriptome in the human melanoma cell line WM793.
2019-04-03 | GSE128955 | GEO
Project description:TWIST1, a basic helix-loop-helix transcription factor is essential for the development of cranial mesoderm and cranial neural crest-derived craniofacial structures. Our previous work showed that, in the absence of TWIST1, some cells within the cranial mesoderm adopt an abnormal epithelial configuration. Here, we show by transcriptome analysis that loss of TWIST1 in the cranial mesoderm is accompanied by a reduction in the expression of genes that are associated with cell-extracellular matrix interactions and the acquisition of mesenchymal characteristics. By comparing the transcriptional profiles of cranial mesoderm-specific Twist1 loss-of-function mutant and control mouse embryos, we identified a set of genes that are both TWIST1-dependent and predominantly expressed in the mesoderm. By ChIP-seq in a cell line model of a TWIST1-dependent mesenchymal state, we identified, among the downstream genes, three direct transcriptional targets of TWIST1: Ddr2, Pcolce and Tgfbi. Our findings show that the mesenchymal properties of the cranial mesoderm is likely to be regulated by a network of TWIST1 targets genes that influence the extracellular matrix and cell-matrix interactions, and collectively they are required for the morphogenesis of the craniofacial structures. Chromatin extracts were subject to chromatin immunoprecipitation with anti TWIST1 monoclonal antibody (ChIP-seq). Input chromatin, not subject to ChIP was used as the negative control. Two independent replicate experiments were performed. Purified, immunoprecipitated DNA was sequenced at Australian Genome Research facility.
2016-08-23 | E-GEOD-80662 | biostudies-arrayexpress
Project description:In this study, merging in silico transcriptomic data and in situ TMA studies, we first highlighted the clinical significance and the value as prognostic factors of the embryonic TFs TWIST1 and TWIST2, thus linking their level of expression with the outcome of NB patients. Secondly, using NB cells knocked out for the TWIST1 protein, we studied the biological impact of TWIST1 in tumors xenografts. The expression of TWIST1 was associated with enhanced primary and secondary tumor growth capacity in immunocompromised mice. Furthermore, tumors expressing TWIST1 were portrayed by a more aggressive phenotype, characterized by the presence of spindle shaped cells and the destruction of the ECM collagen fibers. Finally, the transcriptional signature deregulated by TWIST1 was found to have a clinical significance in human primary tumors and resulted to be able to activate the TME in ortho-derived xenograft. This dataset reports analyses that studied the impact of knockout of the TWIST1 protein on the secretome of the neuroblastoma cell line mentioned above.
2022-01-10 | PXD024200 | Pride
Project description:Twist1 variants including wildtype Twist1, a non-phosphorylatable mutant Twist1/S42A and a phospho-mimicking mutant Twist1/S42D were expressed in 4T1 cells in which the endogenous Twist1 was depleted. We wanted to use microarray analysis to evaluate those genes that are differentially regulated by Twist1 variants.
2012-05-01 | GSE29754 | GEO
Project description:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare NGS-derived suture transcriptome profiling (RNA-seq) among wild type, Twist1+/- and Twist1+/- with suture regeneration surgery mice Methods: Suture mRNA profiles from one week after induction of seven-month-old wild type, Twist1+/- and Twist1+/- with suture regeneration surgery mice were generated by deep sequencing, in triplicate, using Illumina NextSeq500. Results: Using an optimized data analysis workflow, we mapped about 70 million sequence reads per sample to the mouse genome ( mm10) and identified 43,644 transcripts in the suture of wild type, Twist1+/- and Twist1+/- with suture regeneration surgery mice with Partek E/M workflow.
2020-08-04 | GSE155562 | GEO
Project description:Twist1 encodes a basic helix-loop-helix (bHLH) transcription factor and is a key regulator of craniofacial development. Mutations of TWIST1 gene in human are associated with Saethre-Chotzen syndrome (SCS), a developmental disorder characterized by facial and skull malformations, which are phenocopied by Twist1-null heterozygous mice. Mechanisms that dictate the tissue-specificity of Twist1 in regulating distinct transcriptional targets in different craniofacial cell types remain to be determined. Our work using mass-spectrometry and co-expression analysis in cell lines and embryonic head tissues has revealed that the most prevalent forms of TWIST1 were homodimers and heterodimers with E-proteins (TCF3,TCF4 and TCF12). RNA-seq analysis of embryoid bodies expressing tethered TWIST-E-protein dimers, and ChIP-seq profiling of TWIST1 genome-wide binding sites revealed mechanisms of TWIST1 functional regulation. This study highlighted the pleiotropic roles of TWIST1 dimers in development and revealed a potential molecular mechanism underpinning Twist1-related developmental defects of craniofacial tissues.
2020-03-12 | GSE130253 | GEO
Project description:The basic helix-loop-helix transcription factor Twist1 has a well-documented role in mesenchymal populations of the developing embryo, such as endocardial cushion (ECC) mesenchymal cells and limb buds, and during cancer development and progression. Whether Twist1 regulates the same transcriptional targets in different cell types has yet to be investigated. Through chromatin immunoprecipitation followed by sequencing (Chip-seq) analysis, the cell type-specific genome-wide occupancy of Twist1 was investigated in ECCs, limb buds and mouse peripheral nerve sheath tumor (PNST) cells. Twist1 binds mainly in a cell type-specific manner, with very few common genomic regions occupied by Twist1 in different cell types. Genes associated with binding peaks in each cell type are related to known Twist1 cellular functions in ECCs, limb buds, and cancer cells. We found that cell type-specific binding of Twist1 may be influenced by histone modifications or co-factors. Binding regions were located in several Wnt pathway associated genes, supporting a link between Twist1 and Wnt signalling in ECCs, limb buds, and PNST cells. These data suggest that similar functions are regulated by Twist1 in ECCs, limb buds, and PNST cells in a cell type-specific manner, and provide insights into possible mechanisms utilized for cell type-specificity of Twist1 binding. We compare Twist1 genome occupancy in mouse embryonic day (E) 12.5 endocardial cushion mesenchymal cells, E10.5 forelimb buds, and a mouse peripheral nerve sheath tumor cell line.
2014-10-02 | E-GEOD-50111 | biostudies-arrayexpress
Project description:Twist1 variants including wildtype Twist1, a non-phosphorylatable mutant Twist1/S42A and a phospho-mimicking mutant Twist1/S42D were expressed in 4T1 cells in which the endogenous Twist1 was depleted. We wanted to use microarray analysis to evaluate those genes that are differentially regulated by Twist1 variants. All cell lines were grown to 70% confluency and total RNA was isolated with Qiagen kit. Each sample was prepared as triplicates. Parental 4T1 cells were used as control.
2012-04-30 | E-GEOD-29754 | biostudies-arrayexpress
Project description:The basic helix-loop-helix transcriptional repressor twist1, as an antagonist of nuclear factor κB (NF-κB)-dependent cytokine expression, is involved in the regulation of inflammation-induced immunopathology. We could show that twist1 is expressed by activated T helper (Th) 1 effector memory cells. Induction of twist1 in Th cells is dependent on NF-κB, nuclear factor of activated T cells (NFAT), and interleukin (IL)-12 signaling via signal transducer and activator of transcription (STAT) 4. Expression of twist1 is transient following T-cell receptor engagement, and increases upon repeated stimulation of Th1 cells. Imprinting for enhanced twist1 expression is characteristic of repeatedly restimulated effector memory Th cells and thus of the pathogenic memory Th cells of chronic inflammation. Th lymphocytes from the inflamed joint or gut tissue of patients with rheumatic diseases, Crohn’s disease or ulcerative colitis express high levels of twist1. Expression of twist1 in Th1 lymphocytes limits the expression of the cytokines interferon-γ, IL-2 and tumor necrosis factor-α, and ameliorates Th1-mediated immunopathology in delayed-type hypersensitivity and antigen-induced arthritis. In order to identify the effect of twist1 expression on the function of Th cells, twist1 was ectopically expressed and the transcriptome was compared to empty-virus infected control cells. In addition, this experiment allows for the identification of genes regulated by the transcription factor twist1.
2008-05-24 | GSE11533 | GEO