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GSE45295
Homo sapiens
9 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The mammalian HIRA/UBN1/ASF1a complex is a histone chaperone complex that is conserved from yeast (Saccharomyces cerevisiae) to humans. This complex preferentially deposits the histone variant H3.3 into chromatin in a DNA replication-independent manner and is implicated in diverse chromatin regu- latory events from gene activation to heterochromatinization. In yeast, the orthologous complex consists of three Hir proteins (Hir1p, Hir2p, and Hir3p), Hpc2p, and Asf1p. Yeast Hir3p has weak homology to CABIN1, a fourth member of the human complex, suggesting that Hir3p and CABIN1 may be orthologs. Here we show that HIRA and CABIN1 interact at ectopic and endogenous levels of expression in cells, and we isolate the quaternary HIRA/UBN1/CABIN1/ASF1a (HUCA) complex, assembled from recombinant proteins. Mutational analyses support the view that HIRA acts as a scaffold to bring together UBN1, ASF1a, and CABIN1 into a quaternary complex. We show that, like HIRA, UBN1, and ASF1a, CABIN1 is involved in heterochromatinization of the genome of senescent human cells. Moreover, in proliferating cells, HIRA and CABIN1 regulate overlapping sets of genes, and these genes are enriched in the histone variant H3.3. In sum, these data demonstrate that CABIN1 is a functional member of the human HUCA complex and so is the likely ortholog of yeast Hir3p.
Publication Title
Human CABIN1 is a functional member of the human HIRA/UBN1/ASF1a histone H3.3 chaperone complex.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Neuroendocrine tumors (NETs) often harbor loss-of-function mutations in Daxx gene. Daxx interacts with several partners to regulate cellular processes and gene expression.
Publication Title
Menin and Daxx Interact to Suppress Neuroendocrine Tumors through Epigenetic Control of the Membrane Metallo-Endopeptidase.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Multiple endocrine neoplasia type1 (MEN1), an inherited autosomal dominant syndrome characterized by the development of endocrine tumors including NETs, results from mutation in the MEN1 gene that encodes the protein menin. In mouse models, heterozygous loss of Men1 leads to multiple endocrine tumors with loss of heterozygocity at the Men1 locus. Men1 interacts with several partners to regulate cellular processes and gene expression through regulating histone modification.
Publication Title
Menin and Daxx Interact to Suppress Neuroendocrine Tumors through Epigenetic Control of the Membrane Metallo-Endopeptidase.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The dynamic and reversible acetylation of proteins catalyzed by histone acetyltransferases (HATs) and histone deacetylases (HDACs) was discovered more than 2 decades ago and the enzymatic function of these enzymes are established as a major epigenetic regulatory mechanism of gene transcription. Thus, these epigenetic modifiers are involved in multiple diseases and represent attractive targets for therapeutic intervention. While HDAC inhibitors have been developed and approved by the FDA to treat certain cancers, progress on the development of drug-like HAT inhibitors has lagged. The HAT paralogs p300 and CBP (here called p300/CBP) are key transcriptional co-activators that are essential for a multitude of cellular processes and also implicated in human pathological conditions, including cancer. Current p300/CBP HAT domain inhibitors including natural products and bisubstrate analogs such as Lys-CoA either lack potency and selectivity or suffer from poor cellular permeability. C646 is widely utilized as a tool to inhibit p300/CBP HAT activity, but its off-target activity and reactivity may limit its cellular specificity. Here, we describe A-485 as a potent, selective and drug-like p300/CBP catalytic inhibitor. We show the first high resolution (1.95) co-crystal structure of a pharmacologically active small molecule (A-485) bound to the catalytic active site of p300 HAT domain and demonstrate that A-485 is an acetyl-CoA competitive inhibitor of p300/CBP. A-485 selectively inhibited proliferation across lineage-specific tumor types, including several hematological malignancies and androgen receptor-positive prostate cancer. A-485 robustly inhibited the androgen receptor transcriptional program in both androgen sensitive and castrate resistant prostate cancer and inhibited tumor growth in a castration resistant xenograft model. These results demonstrate the feasibility of selectively drugging the catalytic activity of histone acetyltransferases, provide the framework for delineating the enzymatic functions of HATs, and pave the way for the development of novel therapeutics targeting HAT activity.
Publication Title
Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours.
Sample Metadata Fields
Cell line
View Samples- Drosophila melanogaster
- 89 Downloadable Samples
NextSeq 500
Description
Developmental neuronal remodeling is an evolutionarily conserved mechanism required for accurate wiring of mature nervous systems. Despite its fundamental role in neurodevelopment and proposed contribution to various neuropsychiatric disorders, the mechanisms instructing remodeling are only partially known. Here, we uncover the fine temporal transcriptional landscape of a stereotypic remodeling event - that of the Drosophila mushroom body ? neurons. To enrich and complement this developmental expression atlas, we also sequenced developing ? neurons perturbed for three key transcription factors known to regulate pruning. Together, these datasets allowed us to construct the developmental and temporal framework of transcriptional modules that together drive remodeling. Moreover, we identified 10 DNA binding proteins that are involved in various aspects of remodeling, and describe their hierarchical relationships. Overall, this study provides the first broad and detailed molecular insight into the complex regulatory dynamics of developmental neuronal remodeling. Overall design: Transcriptional profiling of drosophila ? neurons during development and when perturbed by EcR-DN, E75 RNAi or Sox14 RNAi. Other adult neurons and astrocyte-like cells also sequenced.
Publication Title
Combining Developmental and Perturbation-Seq Uncovers Transcriptional Modules Orchestrating Neuronal Remodeling.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Arabidopsis thaliana
- 7 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Cadmium sulfide quantum dots (CdS QDs) are widely used in novel equipment. The relevance of the research lies in the need to develop risk assessments for nanomaterials, using as basis a model plant species.
Publication Title
Genome-wide approach in Arabidopsis thaliana to assess the toxicity of cadmium sulfide quantum dots.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
The aim of this experiment was to investigate differential gene expression in splenocytes stimulated with BCG from nave and BCG vaccinated mice. The differences between nave and BCG vaccinated mice might indicate the mechanisms by which BCG vaccination confers an enhanced ability of splenocytes from BCG vaccinated mice to inhibit growth of BCG in splenocyte cultures as compared with splenocytes from naive animals.
Publication Title
Mycobacterial growth inhibition in murine splenocytes as a surrogate for protection against Mycobacterium tuberculosis (M. tb).
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Transient expression of two factors, or from Oct4 alone, resulted in efficient generation of human iPSCs. The reprogramming strategy described revealed a potential transcriptional signature for human iPSCs yet retaining the gene expression of donor cells in human reprogrammed cells free of viral and transgene interference.
Publication Title
Transcriptional signature and memory retention of human-induced pluripotent stem cells.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Human medulloblastoma (MB) can be segregated into four major categories based on gene expression patterns: Hedgehog (HH) subtype, Wnt subtype, Group 3, and Group 4. However, they all exhibit strikingly different gene expression profiles from Atypical Teratoid/Rhabdoid Tumor (AT/RT). We re-analyzed published gene expression microarray dataset of pediatric brain tumors to identify a gene expression profile that clearly distinguished human AT/RT from human MB. We used this profile, choosing only genes that have clear murine orthologs, to compare tumors from Snf5F/Fp53L/LGFAP-Cre mice (in C57Bl/6 strain background) with MB from Ptc1+/- mice (in mixed C57Bl/6 and 129Sv strain background). Snf5F/Fp53L/LGFAP-Cre tumors are clearly very different from mouse MB and the markers that distinguish human AT/RT from human MB also distinguish the mouse tumors.
Publication Title
Generation of a mouse model of atypical teratoid/rhabdoid tumor of the central nervous system through combined deletion of Snf5 and p53.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Four vehicle-treated and four HhAntag-treated pancreatic xenograft tumors were profiled for gene expression changes using Affymetrix U133 Plus 2.0 and Affymetrix Mouse Genome 430 2.0 arrays.
Publication Title
A paracrine requirement for hedgehog signalling in cancer.
Sample Metadata Fields
No sample metadata fields
View Samples