Nuclear receptor (NR)-mediated transcription is a dynamic process that is regulated by the binding of distinct ligands that induce conformational changes in the NR. These molecular alterations lead to the recruitment of unique cofactors (coactivators or corepressors) that control the expression of NR-regulated genes. Here, we show that a stretch of proline residues located within the N-terminus of AR is necessary for maximal androgen-mediated prostate cancer cell growth and migration. Furthermore, this polyproline domain is necessary for the expression of a subset of AR-target genes, but is dispensable for classical AR-mediated gene transcription. Using T7 phage display, we subsequently identified a novel AR-interacting protein, SH3YL1, whose interaction with AR is dependent upon this polyproline domain. Like the AR polyproline domain, SH3YL1 was required for maximal androgen-mediated cell growth and migration. Microarray analysis revealed that SH3YL1 also regulated a subset of AR-modulated genes. Correspondingly, we identified ubinuclein1 (UBN1), a key member of a histone H3.3 chaperone complex, as a transcriptional target of AR/SH3YL1. Moreover, UBN1 was necessary for maximal androgen-mediated proliferation and migration. Collectively, our data link a specific surface located within ARs N-terminus to the recruitment of a novel cofactor, SH3YL1, which is required for the androgen-mediated expression of UBN1. Importantly, this signaling network was important for both androgen-mediated prostate cancer cell growth and migration. This work is significant because it could aid in the development of selective androgen receptor modulators (SARMs) and have therapeutic implications for AR-driven diseases.
Identification of a Novel Coregulator, SH3YL1, That Interacts With the Androgen Receptor N-Terminus.
Specimen part
View SamplesThe aim of this study was to assess the impact of oocyte competence on subsequent fertility. Based on knowledge already accessible in mammals and on bioinformatics tools including the chicken genome sequence, we focused on the expression of genes involved in the processes of fertilization and of early embryo development. The study was performed using two complementary approaches: a descriptive study of standard laying hens and then a differential study performed with hens from experimental lines expressing broad variations of achieved fertility (approximately 20 per cent). A differential kinetic study is performed on INRA lines selected on the basis of their fertility potential in purpose of hopefully access gene markers of fertility performance.
Identification of germinal disk region derived genes potentially involved in hen fertility.
No sample metadata fields
View SamplesThe aim of this study was to assess the impact of oocyte competence on subsequent fertility. Based on knowledge already accessible in mammals and on bioinformatics tools including the chicken genome sequence, we focused on the expression of genes involved in the processes of fertilization and of early embryo development.
Search for the genes involved in oocyte maturation and early embryo development in the hen.
No sample metadata fields
View SamplesRNA-seq analysis was performed between WT and alphaT-cat KO mouse cerebella aiming to discover gene transcripts altered by the loss of alphaT-cat These altered gene transcripts could be associated with several neurologic disease-relevant pathways Overall design: Total RNA extracted of cerebellar tissue (n=3) from the brains of WT ad alphaT-cat KO mice
αT-catenin in restricted brain cell types and its potential connection to autism.
Specimen part, Subject
View SamplesRNA-SEQ profiling of dopaminergic neurons from the substantia nigra pars compacta and ventral tegmental area regions of the mouse mid-brain Overall design: Murine midbrain dopaminergic neurons from the SNpc and VTA regions
Identification of neurodegenerative factors using translatome-regulatory network analysis.
No sample metadata fields
View SamplesRNA-SEQ of dopaminergic neurons from the mid-brain of mice that received one daily intraperitoneal injection of MPTP-HCl (30 mg/kg free base per day) or saline for five consecutive days. Samples were taken 4 days. Overall design: Murine midbrain dopaminergic neurons that were treated with MPTP-HCl
Identification of neurodegenerative factors using translatome-regulatory network analysis.
No sample metadata fields
View SamplesNaïve CD4 T cells differentiate into functionally diverse subsets of T helper (Th) cells. Gene expression profiling has the capacity to pinpoint factors that regulate subset differentiation and function, however obtaining transcriptional profiles of pure populations has been challenging. We performed single cell RNA-Sequencing (scRNA-Seq) of T helper cells from lymph node, lung and airways in a mouse model of asthma. scRNA-Seq resolved transcriptional profiles of naïve CD4 T, Th1, Th2, Treg cells and various activated states including a population responding to type I interferons. A trajectory for Th2 cell differentiation was delineated over time, with Th2 cells acquiring follicular T helper cell characteristics in the lung-draining lymph node before undergoing further modifications in the lung. A feature of airway Th2 cells was their enrichment for genes associated with lipid metabolism and experiments with blockers of key metabolic pathways supported roles for glucose and lipid metabolism in Th2 cell differentiation. Overall design: Mice were sentized and challanged with HDM extract intranasally. scRNA-Seq was performed in 384-well format. The relevant organs (either BAL, lung or mLN) were isolated, rapidly processed, stained for a panel of surface markers and single cell sorted within approximately 90 minutes of organ harvest. In total 764 memory T helper cells (CD3+CD4+CD44+) were sorted directly into lysis buffer using a BD Influx from two independent mice 15 days after sensitization and challenge with HDM as described above. In addition, 50 naïve T Helper cells (CD3+CD4+CD62LhiCD44lo), 50 Treg cells (CD3+CD4+CD25hi) from mLN of a mouse not exposed to HDM; 200 ST2+ mLN and 82 ST2+ lung T helper cells (CD3+CD4+CD44+ST2+CD25-) were sort purified at day 10 of the HDM model. SMART-Seq2 libraries were prepared using the method described in Picelli et al. (Nature Methods 2013) by the Eukaryotic Single Cell Genomics national facility at SciLife Laboratory, Stockholm.
Single-Cell RNA Sequencing of the T Helper Cell Response to House Dust Mites Defines a Distinct Gene Expression Signature in Airway Th2 Cells.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease.
Treatment
View SamplesPatterns of gene expression in the aged entorhinal cortex and hippocampus were examined one month after entorhinal administration of BDNF lentivirus. Whole-genome patterns of expression were examined using Affymetrix arrays four weeks after entorhinal injection of lentiviral-BDNF or GFP injection compared to control subjects.
Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease.
Treatment
View SamplesTranslation and mRNA degradation are intimately connected, yet the mechanisms that regulate them are not fully understood. Here we examine the regulation of translation and mRNA stability in mouse embryonic stem cells (ESCs) and during differentiation. In contrast to previous reports, we found that transcriptional changes account for most of the molecular changes during ESC differentiation. Within ESCs translation level and mRNA stability are positively correlated. The RNA-binding protein DDX6 has been implicated in processes involving both translational repression and mRNA destabilization; in yeast DDX6 connects codon optimality and mRNA stability and in mammals DDX6 is involved in microRNA-mediated repression. We generated DDX6 KO ESCs and found that while there was minimal connection between codon usage and stability changes, the loss of DDX6 leads to the translational depression of microRNA targets. Surprisingly, the translational derepression of microRNA targets occurs without affecting mRNA stability. Furthermore, DDX6 KO ESCs share overlapping phenotypes and global molecular changes with ESCs that completely lack all microRNAs. Together our results demonstrate that the loss of DDX6 decouples the two forms of microRNA induced repression and emphasize that translational repression by microRNAs is underappreciated. Overall design: 4-thiouridine (4su) metabolic labeling was performed on mouse embryonic stem cells (ESCs) and Epiblast like cells (EpiLCs).
Decoupling the impact of microRNAs on translational repression versus RNA degradation in embryonic stem cells.
Specimen part, Disease, Subject
View Samples