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SRP034657
Homo sapiens
2 Downloadable Samples
IlluminaGenomeAnalyzerII
Description
ERa is essential for the anti-proliferative response of breast cancer cells not only to estrogen antagonists, but also to estrogen withdrawal by means of aromatase inhibitors. We explored here one of the simplest explanation for this, consisting in the possibility that ERa may have a wide genomic function in absence of ligands. The genomic binding of ERa in the complete absence of estrogen was then studied using hormone-dependent MCF7 cells, by chromatin immunoprecipitation sequencing. From these data, 4.2K highly significant binding events were identified, which were further confirmed by comparing binding events in cells expressing ERa to cells silenced for ERa. Apo-ERa binding sites were distributed close to genes with functions associated to cell growth and epithelial maintenance and show significant overlap with binding of other transcription factors important for luminal epithelial breast cancer. Interestingly, we found that upon ERa silencing cognate gene transcription in absence of estrogen is downregulated and this is accompanied by increased H27Kme3 at ERa binding sites. RNA-Seq experiments showed that unliganded ERa controls basal transcription widely, including both coding and noncoding transcripts. Genes affected by ERa silencing can be easily functionally related to mammary epithelium differentiation and maintenance, especially when considering downregulated genes. Additional functions related to inflammatory and immune response was observed. Our data unravel unexpected actions of ERa in breast cancer cells and provide a novel framework to understand success and failure of hormone therapy in breast cancer. Overall design: Examination of unligandend estrogen receptor alpha (aERa) DNA interactions in control and aERa siRNA treated MCF7 cells.
Publication Title
Dissecting the genomic activity of a transcriptional regulator by the integrative analysis of omics data.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
The cellular response to genotoxic stress is mediated by a well-characterized network of DNA surveillance pathways. The contribution of posttranscriptional gene regulatory networks to the DNA damage response (DDR) has not been extensively studied. Here, we systematically identified RNA-binding proteins differentially interacting with polyadenylated transcripts upon exposure of human breast carcinoma cells to ionizing irradiation (IR). Interestingly, more than 260 proteins including many nucleolar proteins showed increased binding to poly(A) RNA in IR-exposed cells. The functional analysis of DDX54, a candidate genotoxic stress responsive RNA helicase, revealed that this protein is an immediate-to-early DDR regulator required for the splicing efficacy of its target IR-induced pre-mRNAs. Upon IR exposure, DDX54 acts by increased interaction with a well defined class of pre-mRNAs which harbor introns with weak acceptor splice sites, as well as by protein-protein contacts within components of U2 snRNP and spliceosomal B complex, resulting in lower intron retention and higher processing rates of its target transcripts. Since DDX54 promotes survival after exposure to IR its expression and/or mutation rate may impact DDR-related pathologies. Our work indicates the relevance of many uncharacterized RBPs potentially involved in the DDR. Overall design: Gene expression profiling of MCF-7 cells upon DDX54 knockdown exposed to ionizing radiation
Publication Title
DDX54 regulates transcriptome dynamics during DNA damage response.
Sample Metadata Fields
Specimen part, Cell line, Subject, Time
View Samples- Homo sapiens
- 24 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Human myelopoiesis is an exciting biological model for cellular differentiation since it represents a plastic process where pluripotent stem cells gradually limit their differentiation potential, generating different precursor cells which finally evolve into distinct terminally differentiated cells. This study aimed at investigating the genomic expression during myeloid differentiation through a computational approach that integrates gene expression profiles with functional information and genome organization. The genomic distribution of myelopoiesis genes was investigated integrating transcriptional and functional characteristics of genes. The analysis of genomic expression during human myelopoiesis using an integrative computational approach allowed discovering important relationships between genomic position, biological function and expression patterns and highlighting chromatin domains, including genes with coordinated expression and lineage-specific functions.
Publication Title
Motif discovery in promoters of genes co-localized and co-expressed during myeloid cells differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Time-series analysis of response to ribosome 28s damage at gene expression level
Publication Title
Early Response to the Plant Toxin Stenodactylin in Acute Myeloid Leukemia Cells Involves Inflammatory and Apoptotic Signaling.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Human myelopoiesis is an exciting biological model for cellular differentiation since it represents a plastic process where pluripotent stem cells gradually limit their differentiation potential, generating different precursor cells which finally evolve into distinct terminally differentiated cells. This study aimed at investigating the genomic expression during myeloid differentiation through a computational approach that integrates gene expression profiles with functional information and genome organization. The genomic distribution of myelopoiesis genes was investigated integrating transcriptional and functional characteristics of genes. The analysis of genomic expression during human myelopoiesis using an integrative computational approach allowed discovering important relationships between genomic position, biological function and expression patterns and highlighting chromatin domains, including genes with coordinated expression and lineage-specific functions.
Publication Title
Motif discovery in promoters of genes co-localized and co-expressed during myeloid cells differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Total RNAs were cloned from wt, Dis3L2 and Tailor mutant testis tissues to study the role of Tailor and Dis3L2 TUTase/nuclease complex Overall design: Replicated total RNA samples from Dis3L2 and Tailor single mutant, and Dis3L2/Tailor double mutant and WT (w1118) testes
Publication Title
Characterization of a TUTase/RNase complex required for <i>Drosophila</i> gametogenesis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Whole-genome expression studies in peripheral tissues of patients affected by schizophrenia (SCZ) can provide new insights into the molecular basis of the disorder and innovative biomarkers that may be of great usefulness in the clinical practice. Recent evidence suggests that skin fibroblasts could represent a non-neural peripheral model useful to investigate molecular alterations in psychiatric disorders.
Publication Title
Altered gene expression in schizophrenia: findings from transcriptional signatures in fibroblasts and blood.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
The objective of this study was to identify transcriptional changes differentially regulated by GDF11 stimulation compared to TGFB1
Publication Title
Tumor-Suppressor Inactivation of GDF11 Occurs by Precursor Sequestration in Triple-Negative Breast Cancer.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 246 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Disentangling the microRNA regulatory milieu in multiple myeloma: integrative genomics analysis outlines mixed miRNA-TF circuits and pathway-derived networks modulated in t(4;14) patients.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 93 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The identification of deregulated miRNA in multiple myeloma (MM) has progressively added a further level of complexity to MM biology. In the present study, we take virtue of in silico integrative genomics analysis to generate an unprecedented global view of the transcriptional regulatory networks modulated in MM to define microRNAs impacting in regulatory circuits with potential functional and clinical relevance. miRNA and gene expression profiles in two large representative MM datasets, available from retrospective and prospective clinical trials and encompassing a total of 249 patients at diagnosis, were analyzed by means of two robust computational procedure to identify (i) relevant miRNA/transcription factors/target gene circuits in the disease and (ii) highly modulated miRNA-gene networks in those pathways enriched with miRNA-target gene interactions in specific MM subgroups. The analysis reinforced the pivotal role the miRNA cluster miR-99b/let-7e/miR-125a, specifically deregulated in MM patients with t(4;14) translocation, and disentangled its major relationships with transcriptional relevance. Integrated pathway analyses performed on the expression data of the MM patients stratified according to t(4;14) further allowed to define the pathway composed by the interactions that mainly characterize this MM subset and unravel connected pathways with putative role in the tumor biology.
Publication Title
Disentangling the microRNA regulatory milieu in multiple myeloma: integrative genomics analysis outlines mixed miRNA-TF circuits and pathway-derived networks modulated in t(4;14) patients.
Sample Metadata Fields
Disease, Disease stage
View Samples