Similar Datasets
Project description:We aim to explore the types and expression of RNA in iPSC-RPE cells, iRPE cells, hUCMSCs and ARPE19.
2024-01-01 | GSE194365 | GEO
Project description:MITF is the master regulator of the melanocyte lineage and a melanoma lineage oncogene. It controls a wide range of target genes fulfilling many distinct functions, but relatively little is known about how its DNA-binding is regulated to select the correct target genes. The datasets presented here were used investigate the effects of MAPK signaling-induced MITF-acetylation on MITF activity in melanoma cells through ChIP-Seq of wild-type and acetyl-mutant MITF.
2021-02-12 | GSE77437 | GEO
Project description:The aim of this study was to analyze the pan-transcriptional regulations induced in hiPSC-derived RPE (iRPE) cells by corticoids with specific inhibitors of their receptors to decipher specific genes regulated by MR or GR activation. Cells were seeded at P3 in cell culture plastic dishes. On day 35, one week prior to corticosteroids treatments, RDMw/oA medium was remove and iRPE cells were incubated in experimental corticosteroid-free medium (DMEM, high glucose, HEPES, no phenol red, 10% Fetal Bovine Serum, charcoal stripped). On day 42, iRPE cells were treated for 24 h with the following corticosteroids treatments: aldosterone (10-7 M), cortisol (10-7 M) and cortisol (10-7 M) plus RU-486 (10-5 M). As corticosteroids were dissolved in ethanol (EtOH) or methanol (MeOH) control cells were treated with 0.1% EtOH or MeOH in medium. Total RNA samples extracted from iRPE were sequenced at the iGenSeq transcriptomic platform of the Brain and Spine Institute (ICM, Paris, France). RNA quality was checked by capillary electrophoresis (Agilent 2100 Bioanalyzer system) and RNA with integrity numbers (RIN) ranging from 7.8 to 8.2 was accepted for library generation. Quality of raw data has been evaluated with FastQC. Librairies were prepared with Roche KAPA mRNA HyperPrep kit and sequenced with the Illumina NextSeq 500 Sequencing system using NextSeq 500 High Output Kit v2 (150 cycles), 400 millions of reads, 50Gbases. Star v2.5.3a has been used to align reads on reference genome hg19 using standard options. Quantification of gene and isoform abundances has been done with rsem 1.2.28, prior to normalization on library size with edgeR bioconductor package. Finally, differential analysis has been also conducted with edgeR. Multiple hypothesis adjusted p-values were calculated with the Benjamini-Hochberg procedure to control FDR. We identified genes differentially regulated by MR and GR, and those regulated by both MR and GR activation in hiPSC-RPE cells.
2021-09-06 | GSE172478 | GEO
Project description:Homeodomain transcription factors (HD TFs) are instrumental to vertebrate development. Mutations in HD TFs have been linked to human diseases, but their pathogenic mechanisms remain elusive. Here we use Cone-Rod Homeobox (CRX) as a model to decipher the disease-causing mechanisms of two HD mutations, p.E80A and p.K88N, that produce severe dominant retinopathies. Through integrated analysis of molecular and functional evidence in vitro and in knock-in mouse models, we uncover two novel gain-of-function mechanisms: p.E80A increases transactivation of canonical CRX target genes in developing photoreceptors; p.K88N alters CRX DNA-binding specificity resulting in binding at ectopic sites and severe perturbation of CRX target gene expression. Both mechanisms produce novel retinal morphological defects and hinders photoreceptor maturation distinct from loss-of-function models. This study reveals the distinct roles of E80 and K88 residues in CRX HD regulatory functions and emphasizes the importance of transcriptional precision in normal development.
2023-11-08 | GSE223657 | GEO
Project description:Great efforts have been made to identify key molecular aberrations that sustain growth and confer resistance to androgen deprivation therapy (ADT) in advanced prostate cancer (PC), and yet PC remains a lethal disease. Recent years have witnessed the discovery of several master regulator transcription factors that enhance lethal PC aggressiveness and provide actionable targets that may improve patient survival. Here we explore the role of the microphthalmia transcription factor (MITF) in lethal prostate cancer. To identify the mechanisms through which MITF mododulates prostate cancer aggressiveness, we knock-down MITF in three prostate cancer cell lines to identify the MITF regulated effector gene network contributing to lethal prostate cancer. Methods: We compared global transcription of three prostate cancer cell lines transduced with a siRNA control and 2 siRNAs targetting MITF by RNAseq. Results: RNA-seq of MITF knockdown prostate cancer cells uncovered a trasncriptional network of MITF regulated genes Conclusions: MITF regulates a discrette gene network that contributes to prostate cancer aggressiveness
2023-12-22 | GSE133977 | GEO
Project description:The cone-rod homeobox gene (Crx) encodes Crx, a transcription factor selectively expressed in two cell types, retinal photoreceptors and the melatonin secreting pinealocytes of the pineal gland. In this report the role of Crx in regulating gene expression in the mammalian pineal gland was extended using Affymetrix GeneChip technology. Deletion of Crx results in broad modulation of the mouse pineal transcriptome, including a >2-fold downregulation of 543 genes and a >2-fold upregulation of 745 genes. In addition to Crx, there was a >10-fold downregulation of 13 other genes. Of special interest was the discovery of a link between Crx and the homeobox gene Hoxc4, which was upregulated ~20-fold in the Crx-/- pineal gland. Analysis of night and day expression of genes indicated that a set of 51 genes exhibited differential expression in control animals. Of these genes, only eight were also differentially expressed in Crx-/- animals. This group included Aanat, which encodes the enzyme that controls the daily rhythm in melatonin synthesis in the vertebrate pineal gland. Accordingly, Crx appears to be essential for the 24-hour rhythmic component of expression of some genes in the pineal gland. In the Crx-/- mouse pineal gland, 41 genes exhibited differential night/day expression that was not seen in control animals, suggesting that Crx may function to modulate rhythmic expression of these genes as well. Together, the results of this investigation indicate that Crx broadly modulates the pineal transcriptome, perhaps in part through suppressive effects on expression of the homeobox gene Hoxc4. Pineal glands from control (129sv) mice and Crx-/- mice were collected at ZT6 and ZT20 for RNA extraction and hybridization on Affymetrix mouse 430_2 chip. Each condition were performed as triplicats. SUPPLEMENTARY FILES: The GCOS signal intensity data were analyzed using ChipInspector (Genomatix) version 2.1. FDR= 0, p-value <0.05, cut off=1, region size = 300 bp and 4 and 5 significant probes. Log(2) fold change independently of time of day. Up regulated genes: genes which are up regulated in Crx-/- compared to the control; down regulated genes: genes which are down regulated in Crx-/- compared to the control.
2012-01-01 | E-GEOD-24625 | biostudies-arrayexpress
Project description:MITF and MYC are well‐known oncoproteins and members of the basic helix‐loop‐helix leucine zipper (bHLH‐Zip) family of transcription factors (TFs) recognizing hexamer E‐box motifs. MITF and MYC not only share the core binding motif, but are also the two most highly expressed bHLH‐Zip transcription factors in melanocytes, raising the possibility that they may compete for the same binding sites in select oncogenic targets. Mechanisms determining the distinct and potentially overlapping binding modes of these critical oncoproteins remain uncharacterized. We introduce computational predictive models using local sequence features, including a boosted convolutional decision tree framework, to distinguish MITF vs. MYC‐MAX binding sites with up to 80% accuracy genome wide. Select E‐box locations that can be bound by both MITF and MYC‐MAX form a separate class of MITF binding sites characterized by differential sequence content in the flanking region, diminished interaction with SOX10, higher evolutionary conservation, and less tissue‐specific chromatin organization.
2018-12-14 | GSE115845 | GEO
Project description:We identified histidine triad nucleotide binding protein 1 (HINT1) as a human teneurin-1 ICD interaction partner in a yeast-2 hybrid screen. This interaction was confirmed in human cells, where HINT1 is known to inhibit the transcription of target genes by directly binding to transcription factors at the promoter. In a whole transcriptome analysis of BS149 glioblastoma cells overexpressing the teneurin-1 ICD, several microphthalmia-associated transcription factor (MITF) target genes were found to be up-regulated. Interestingly, MITF is one of the transcription factors inhibited by HINT1. Thus, we directly compare the transcriptomes of MITF versus TEN1-ICD overexpressing BS149 cells in this study, in order to reveal any co-regulated genes. For the whole transcriptome analysis of MITF, cells were transiently transfected in triplicates with either, pcDNA3.1-RFP-HA (negative control) or pcDNA3.1-MITF-RFP-HA. The overexpressing cells were then FACS-sorted directly into RLT lysis buffer (Qiagen) at a 3:1 volume ratio of lysis buffer to cells in PBS, 24 h post-transfection.
2015-02-04 | E-GEOD-61705 | biostudies-arrayexpress
Project description:Calredoxin (CRX) is a calcium (Ca2+)-dependent thioredoxin (TRX) in the chloroplast of Chlamydomonas reinhardtii. To further elucidate the function of CRX, we performed in-depth quantitative proteomics taking advantage of a crx insertional mutant (IMcrx), two CRISPR/Cas9 KO mutants, CRX rescues and wild type strains. These analyses revealed that the chloroplast NADPH-dependent TRX reductase (NTRC) is co-regulated with CRX. Electron transfer measurements revealed that CRX inhibits NADPH-dependent reduction of oxidized chloroplast 2-Cys peroxiredoxin (PRX1) via NTRC and that the function of the NADPH-NTRC complex is under strict control of CRX. Our data also demonstrated via non-reducing SDS-PAGE assays and redox proteomics that PRX1, Transketolase (TRK1), ATPC and Proton Gradient Related like 1 (PGRL1) are more oxidized under high light (HL) conditions in the absence of CRX. The redox tuning of PRX1 and control of the NADPH-NTRC complex via CRX interconnects redox control with active photosynthetic electron transport and metabolism as well as Ca2+ signaling. In this way, an economic use of NADPH for PRX1 reduction is assured. The finding, that in the absence of CRX, light-driven CO2 fixation is severely inhibited under HL conditions underpins the importance of CRX for redox tuning as well as for efficient photosynthesis.
2023-10-04 | PXD038009 | Pride