This SuperSeries is composed of the SubSeries listed below.
Differential Methylation of H3K79 Reveals DOT1L Target Genes and Function in the Cerebellum In Vivo.
Specimen part
View SamplesDOT1L as methyltransferase of H3K79 is implicated in brian development. Here, we further defined DOT1L function in gene expression during cerebellar development using Microarrays. For that we generated Dot1l knockout mice using a Atoh-Cre driver line resulting in a Dot1l knockout within the cerebellum. The RNA of cerebellar tissue of the Dot1l knockout animals was thereby compared to controls. Additionally we compared the RNA levels of cultured CGNP and CGN samples treated with a DOT1L inhibitor versus DMSO treated cells. The data sets reveals potential new gene expression targets of DOT1L in vivo and in vitro, which ensure a correct development of the cerebellum.
Differential Methylation of H3K79 Reveals DOT1L Target Genes and Function in the Cerebellum In Vivo.
Specimen part
View SamplesGenome-wide association studies (GWAS) have identified dozens of genomic loci, whose single nucleotide polymorphisms (SNPs) predispose to prostate cancer (PCa). However, the biological functions of these common genetic variants and the mechanisms to increase disease risk are largely unknown. We integrated chromatin-IP coupled sequencing (ChIP-seq) and microarray expression profiling in the TMPRSS2-ERG gene rearrangement positive DuCaP cell model with the NHGRI GWAS PCa risk SNPs catalog, in an attempt to identify disease susceptibility SNPs localized within functional androgen receptor binding sites (ARBSs). Among the 48 GWAS index SNPs and 2,702 linked SNPs defined by the 1000G project 104 were found to be localized in the AR ChIP-seq peaks. Of these risk SNPs, rs11891426 T/G in the 7th intron of its host gene melanophilin (MLPH) was found located within a putative auxiliary ARE motif, which we found enriched in the neighborhood of canonical ARE motifs. Exchange of T to G attenuated the transcriptional activity of the MLPH-ARBS in a reporter gene assay. The expression of MLPH protein in tissue samples from prostate cancer patients was significantly lower in those with the G compared to the T allele. Moreover, a significant positive correlation of AR and MLPH protein expression levels was also confirmed in tissue samples. These results unravel a hidden link between AR and a functional PCa risk SNP rs11891426, whose allele alteration affects androgen regulation of its host gene MLPH. This study shows the power of integrative studies to pin down functional risk SNPs and justifies further investigations.
Putative Prostate Cancer Risk SNP in an Androgen Receptor-Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites.
Cell line, Treatment, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The BTB and CNC homology 1 (BACH1) target genes are involved in the oxidative stress response and in control of the cell cycle.
Cell line, Time
View SamplesBTB and CNC homology 1 (BACH1) is a heme-binding transcription factor repressing the transcription from a subset of MAF recognition elements (MAREs) at low intracellular heme levels. Upon heme binding, BACH1 is released from the MAREs, resulting in increased expression of antioxidant response genes. To systematically address the gene regulatory networks involving BACH1, we performed knock-down of BACH1 in HEK 293T cells using three independent types of small interfering RNAs followed by transcriptome profiling using microarrays.
The BTB and CNC homology 1 (BACH1) target genes are involved in the oxidative stress response and in control of the cell cycle.
Cell line, Time
View SamplesWe have studied the regulatory potential of MYST1-(MOF)-containing MSL and NSL complexes in mouse embryonic stem cells (ESCs) and neuronal progenitors. We find that both complexes influence transcription by binding to promoters as well as TSS-distal enhancer regions. In contrast to flies, the MSL complex is not enriched on the X chromosome yet it is crucial for mammalian X chromosome regulation as it specifically regulates Tsix ncRNA, the major repressor of Xist lncRNA. MSL depletion leads to severely decreased Tsix expression, reduced REX1 recruitment, and consequently accumulation of Xist RNA in ESCs. The NSL complex provides additional, Tsix-independent repression of Xist by maintaining pluripotency. MSL and NSL complexes therefore act synergistically by using distinct pathways to ensure a fail-safe mechanism for the repression of X inactivation in ESCs. Overall design: We have performed ChIP-seq of KANSL3, MCRS1, MOF, MSL1 and MSL2 in mouse ESCs, and KANSL3, MOF and MSL2 in NPCs, in duplicate and normalised against their inputs. We have also performed RNA-seq following knockdown of Kansl3, Mof, Msl1 and Msl2 mouse embryonic stem cells in triplicate. NB: Kansl3 and Mof knockdown-RNAseq are analyzed against their own scrambled controls, and Msl1 and Msl2 against another scrambled control triplicate. siMCRS1 & siMOF were compared to scrambled1 (scr1) siMsl1 and siMsl2 were compared to scr2 siNsl3 was compared to scr3
MOF-associated complexes ensure stem cell identity and Xist repression.
No sample metadata fields
View SamplesRNA-Seq for Lsd1-deficient TSCs or treated with Lsd1 inhibitor for 24hrs Overall design: TSC were treated with Lsd1 inhibitor or DMSO in stemness conditions for 24hrs; media and inhibitor where replaced every 12hrs along the duration of the experiment; 2 replicates were used for treatment together with 2 control replicates in stemness; DFKZ genomics and proteomics. Please note that strain and targeting strategy had been described in the previous PMID: 24448552 publication
Inactivation of Lsd1 triggers senescence in trophoblast stem cells by induction of Sirt4.
Specimen part, Subject
View SamplesNOD2 is an intracellular receptor for the bacterial cell wall component muramyl dipeptide (MDP) and variants of NOD2 are associated with chronic inflammatory diseases of barrier organs e.g. Crohn disease, asthma and atopic eczema. It is known that activation of NOD2 induces a variety of inflammatory and antibacterial factors. The exact transcriptomal signatures that define the cellular programs downstream of NOD2 activation and the influence of the Crohn-associated variant L1007fsinsC are yet to be defined. To describe the MDP-induced activation program, we analyzed the transcriptomal reactions of isogenic HEK293 cells expressing NOD2wt or NOD2L1007fsinsC to stimulation with MDP. Importantly, a clear loss-of-function could be observed in the cells carrying the Crohn-associated variant L1007fsinsC, while the NOD2wt cells showed differential regulation of growth factors, chemokines and several antagonists of NF-B, e.g. TNFAIP3 (A20) and IER3.
Genome-wide expression profiling identifies an impairment of negative feedback signals in the Crohn's disease-associated NOD2 variant L1007fsinsC.
Cell line, Time
View SamplesWe analyzed the role of MOF in primary MEFs and differentiated podocytes in response to Adriamycin. Mof was deleted in MEFs using the Cre-ERT2 trasgene, while Mof was knockdown in podocytes using shRNA infection. Samples were treated with Adriamycin for 24 hours and gene expression changes analysed. Overall design: Analysis of gene expression changes upon Mof depletion in two cell lines, MEFs and podocytes, with and without Adriamycin
MOF maintains transcriptional programs regulating cellular stress response.
No sample metadata fields
View SamplesET-743 (trabectedin, Yondelis) and PM00104 (Zalypsis) are marine derived compounds that have antitumor activity. ET-743 and PM00104 exposure over sustained periods of treatment will result in the development of drug resistance, but the mechanisms which lead to resistance are not yet understood. Human chondrosarcoma cell lines resistant to ET-743 (CS-1/ER) or PM00104 (CS-1/PR) were established in this study. The CS-1/ER and CS-1/PR exhibited cross resistance to cisplatin and methotrexate but not to doxorubicin. Human Affymetrix Gene Chip arrays were used to examine relative gene expression in these cell lines.
ZNF93 increases resistance to ET-743 (Trabectedin; Yondelis) and PM00104 (Zalypsis) in human cancer cell lines.
Specimen part, Cell line
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