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GSE69042
Homo sapiens
2 Downloadable Samples
Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Background: Central nervous system (CNS) metastases represent a major problem in the treatment of HER2-positive breast cancer due to the disappointing efficacy of HER2-targeted therapies in the brain microenvironment. The antibody-drug conjugate ado-trastuzumab emtansine (T-DM1) has shown efficacy in trastuzumab-resistant systemic breast cancer. Here, we tested the hypothesis that T-DM1 could overcome trastuzumab resistance in preclinical models of brain metastases.
Publication Title
Preclinical Efficacy of Ado-trastuzumab Emtansine in the Brain Microenvironment.
Sample Metadata Fields
Specimen part, Disease, Time
View Samples- Drosophila melanogaster
- 29 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Transcription regulation involves enzyme-mediated changes in chromatin structure. Here, we describe a novel mode of histone crosstalk during gene silencing, in which histone H2A monoubiquitylation is coupled to the removal of histone H3 Lys 36 dimethylation (H3K36me2). This pathway was uncovered through the identification of dRING-associated factors (dRAF), a novel Polycomb group (PcG) silencing complex harboring the histone H2A ubiquitin ligase dRING, PSC and the F-box protein, and demethylase dKDM2. In vivo, dKDM2 shares many transcriptional targets with Polycomb and counteracts the histone methyltransferases TRX and ASH1. Importantly, cellular depletion and in vitro reconstitution assays revealed that dKDM2 not only mediates H3K36me2 demethylation but is also required for efficient H2A ubiquitylation by dRING/PSC. Thus, dRAF removes an active mark from histone H3 and adds a repressive one to H2A. These findings reveal coordinate trans-histone regulation by a PcG complex to mediate gene repression.
Publication Title
dKDM2 couples histone H2A ubiquitylation to histone H3 demethylation during Polycomb group silencing.
Sample Metadata Fields
Cell line
View Samples- Drosophila melanogaster
- 48 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
Identification of Hox gene downstream genes at embryonic stages 11 and 12<br></br><br></br>Functional diversification of body parts is dependent on the formation of specialized structures along the various body axes. In animals, region-specific morphogenesis along the anterior-posterior axis is controlled by a group of conserved transcription factors encoded by the Hox genes. Although it has long been assumed that Hox proteins carry out their function by regulating distinct sets of downstream genes, only a small number of such genes have been found, with very few having direct roles in controlling cellular behavior. We have quantitatively identified hundreds of Hox downstream genes in Drosophila by microarray analysis, and validated many of them by in situ hybridizations on loss- and gain-of-function mutants. One important finding is that Hox proteins, despite their similar DNA binding properties in vitro, have highly specific effects on the transcriptome in vivo, as expression of many downstream genes responds primarily to a single Hox protein. In addition, a large fraction of downstream genes encodes realizator functions, which directly affect morphogenetic processes, such as orientation and rate of cell divisions, cell-cell adhesion and communication, cell shape and migration, or cell death. Focusing on these realizators, we provide a framework for the morphogenesis of the maxillary segment. Since the genomic organization of Hox genes and the interaction of Hox proteins with specific cofactors are conserved in vertebrates and invertebrates, and similar classes of downstream genes are regulated by Hox proteins across the metazoan phylogeny, our findings represent a first step towards a mechanistic understanding of morphological diversification within a species as well as between species.
Publication Title
Comparative analysis of Hox downstream genes in Drosophila.
Sample Metadata Fields
Age, Time
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Glioblastoma multiforme (GBM) is a highly malignant primary central nervous neoplasm characterized by tumor cell invasion, robust angiogenesis, and a mean survival of 15 months. Human cytomegalovirus (HCMV) infection is present in > 90% of GBMs, although the role the virus plays in GBM pathogenesis is unclear. We report here that a majority of human GBM tumors express HCMV pp71, which has previously been found to promote cell cycle progression and viral replication, and that pp71 is expressed preferentially within the CD133+ cancer stem cell-like subpopulation. Overexpression of pp71 in adult neural precursor cells (NPCs) resulted in a dramatic induction of stem cell factor (SCF) gene expression, which has been identified as an important pro-angiogenic factor in GBM.
Publication Title
Cytomegalovirus pp71 protein is expressed in human glioblastoma and promotes pro-angiogenic signaling by activation of stem cell factor.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
Illumina HiSeq 2500
Description
Myocardin-related transcription factors (MRTFs) play a central role in the regulation of actin expression and cytoskeletal dynamics. Stimuli that promote actin polymerization allow for shuttling of MRTFs to the nucleus where they activate serum response factor (SRF), a regulator of actin and other cytoskeletal protein genes. SRF is an essential regulator of skeletal muscle differentiation and numerous components of the muscle sarcomere, but the potential involvement of MRTFs in skeletal muscle development has not been examined. We explored the role of MRTFs in muscle development in vivo by generating mutant mice harboring a skeletal muscle-specific deletion of MRTF-B and a global deletion of MRTF-A. These double knockout (dKO) mice were able to form sarcomeres during embryogenesis. However, the sarcomeres were abnormally small and disorganized, causing skeletal muscle hypoplasia and perinatal lethality. Transcriptome analysis demonstrated dramatic dysregulation of actin genes in MRTF dKO mice, highlighting the importance of MRTFs in actin cycling and myofibrillogenesis. MRTFs were also necessary for the survival of skeletal myoblasts and for the efficient formation of intact myotubes. Our findings reveal a central role for MRTFs in sarcomere formation during skeletal muscle development and point to the potential involvement of these transcriptional coactivators in skeletal myopathies. Overall design: Gene expression profile was generated comparing wild type (WT) and HSA-Cre, MRTF-A/B double knockout mice, by deep seqencing, with three biological replicates, using Illumina HiSeq 2500.
Publication Title
Myocardin-related transcription factors are required for skeletal muscle development.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus, Homo sapiens
- 110 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st), Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Gene expression signature for biliary atresia and a role for interleukin-8 in pathogenesis of experimental disease.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 92 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Liver biopsy samples were obtained from 64 infants with biliary atresia at the time of intraoperative cholangiogram. Liver biopsy samples were obtained from 14 age-matched infants with other causes of intrahepatic cholestasis, and from 7 deceased-donor children. GeneChip Human Gene 1.0 ST Array (Affymetrix, CA) were used to screen mRNAs whose expression was specifically regulated in the livers from patients with biliary atresia.
Publication Title
Gene expression signature for biliary atresia and a role for interleukin-8 in pathogenesis of experimental disease.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Regulation of constitutive and alternative splicing by PRMT5 reveals a role for Mdm4 pre-mRNA in sensing defects in the spliceosomal machinery.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st), Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Newborn Balb/c mice were injected intraperitoneally with 1.5x10^6 fluorescent-forming units (ffu) of type- A Rhesus Rotavirus (RRV) or 0.9% normal saline (NS; control) within 24 hours of birth to induce experimental model of biliary atresia. Extrahepatic bile ducts including gallbladder were microdissected en bloc at 3, 7 and 14 days after RRV or saline injections. GeneChip Mouse Gene 1.0 ST Array (Affymetrix, CA) were used to screen mRNAs whose expression was differently regulated after RRV challenge compared to normal saline controls.
Publication Title
Gene expression signature for biliary atresia and a role for interleukin-8 in pathogenesis of experimental disease.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Protein Arginine MethylTransferase 5 (PRMT5) is known to mediate epigenetic control on chromatin and to functionally regulate components of the splicing machinery. In this study we show that selective deletion of PRMT5 in different organs leads to cell cycle arrest and apoptosis. At the molecular level, PRMT5 depletion results in reduced methylation of Sm proteins, aberrant constitutive splicing and in the Alternative Splicing (AS) of specific mRNAs. We identify Mdm4 as one of these mRNAs, which due to its weak 5-Donor site, acts as a sensor of splicing defects and transduces the signal to activate the p53 response, providing a mechanistic explanation of the phenotype observed in PRMT5 conditional knockout mice. Our data demonstrate a key role of PRMT5, together with p53, as guardians of the transcriptome. This will have fundamental implications in our understanding of PRMT5 activity, both in physiological conditions, as well as pathological conditions, including cancer and neurological diseases.
Publication Title
Regulation of constitutive and alternative splicing by PRMT5 reveals a role for Mdm4 pre-mRNA in sensing defects in the spliceosomal machinery.
Sample Metadata Fields
Specimen part, Treatment
View Samples