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GSE46645
Mus musculus
10 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Precise nucleosome-positioning patterns at promoters are thought to be crucial for faithful transcriptional regulation. However, the mechanisms by which these patterns are established and dynamically maintained and subsequently contribute to transcriptional control are poorly understood. The Swi/Snf (Baf) chromatin remodeling complex is a master developmental regulator and tumor suppressor that is capable of mobilizing nucleosomes in biochemical assays. Yet, its role in establishing the nucleosome landscape in vivo is unclear. Here we have inactivated Snf5 and Brg1, core subunits of the mammalian Swi/Snf complex, to evaluate their effects on chromatin structure and transcription levels genome-wide. We find that inactivation of either subunit leads to disruptions of specific nucleosome patterning combined with a loss of overall nucleosome occupancy at a large number of promoters, regardless of their association with CpG islands. These rearrangements are accompanied by gene expression changes that promote cell proliferation. Collectively, these findings define a direct relationship between chromatin-remodeling complexes, chromatin structure, and transcriptional regulation.
Publication Title
Swi/Snf chromatin remodeling/tumor suppressor complex establishes nucleosome occupancy at target promoters.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 4 Downloadable Samples
IlluminaHiSeq4000
Description
We report high-throughput profiling of gene expression from whole zebrafish ventricles. We profile mRNA in uninjured ventricles and those undergoing regeneration 14 days after genetic ablation. This study provides a framework for understanding transcriptional changes during adult models of regeneration. Overall design: Examination of gene expression in cardiomyocytes under different states of proliferation.
Publication Title
Resolving Heart Regeneration by Replacement Histone Profiling.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
mRNA expression levels were determined by NGS for wildtype larvae as well as for larvae lacking HP1a [Su(var)205^04/Su(var)205^05 transheterozygotes]. Overall design: RNA samples from wildtype (OR) and HP1a mutant third instar larvae were examined, using duplicate biological samples and Illumina NGS.
Publication Title
Enrichment of HP1a on Drosophila chromosome 4 genes creates an alternate chromatin structure critical for regulation in this heterochromatic domain.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 34 Downloadable Samples
- IlluminaHiSeq2000
Description
SMARCB1 (SNF5/INI1/BAF47), a core subunit of the SWI/SNF (BAF) chromatin remodeling complex, is inactivated in nearly all pediatric rhabdoid tumors. These aggressive cancers are among the most genomically stable, suggesting an epigenetic mechanism by which SMARCB1 loss drives transformation. Here, we show that despite indistinguishable mutational landscapes, human RTs show distinct enhancer H3K27ac signatures, which reveal remnants of differentiation programs. We show that SMARCB1 is required for the integrity of SWI/SNF complexes and that its loss alters enhancer targeting markedly impairing SWI/SNF binding to typical enhancers, particularly those required for differentiation, while maintaining SWI/SNF binding at super-enhancers. We show that these retained super-enhancers are essential for rhabdoid tumor survival, including some that are shared across all subtypes, such as SPRY1, and other lineage-specific super-enhancers like SOX2 in brain-derived RTs. Taken together, our findings reveal a novel chromatin-based epigenetic mechanism underlying the tumor suppressive activity of SMARCB1. Overall design: RNA-seq in six Smarcb1 deficient rhabdoid tumor cell lines, before and after Smarcb1 re-expression.
Publication Title
SMARCB1-mediated SWI/SNF complex function is essential for enhancer regulation.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 8 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Sequence-specific targeting of dosage compensation in Drosophila favors an active chromatin context.
Sample Metadata Fields
Cell line
View Samples- Drosophila melanogaster
- 8 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
The Drosophila MSL complex mediates dosage compensation by increasing transcription of the single X chromosome in males approximately two-fold. This is accomplished through recognition of the X chromosome and subsequent acetylation of histone H4K16 on X-linked genes. Initial binding to the X is thought to occur at a subset of sites. However, the consensus sequence motif of entry sites (MSL recognition element or MRE) is only slightly enriched on the X (~2 fold), and only a fraction of them is utilized by the MSL complex. Here we ask whether chromatin context could distinguish between utilized and non-utilized copies of the motif, by comparing their relative enrichment for histone modifications and chromosomal proteins mapped in the NHGRI modENCODE project. Through a comparative analysis of the chromatin features in male S2 cells, which contain MSL complex, and female Kc cells, which lack the complex, we find that the presence of active chromatin modifications, together with an elevated local GC content in surrounding sequence, has strong predictive value for functional MSL entry sites, independent of MSL binding. We tested these sites for function in Kc cells by RNAi knockdown of Sxl, resulting in induction of MSL complex. We show that ectopic MSL expression in Kc cells leads to H4K16 acetylation around these sites, and a relative increase in X chromosome transcription. Collectively, our results support a model in which a pre-existing active chromatin environment, coincident with H3K36me3, contributes to MSL entry site selection. The consequences of MSL targeting of the male X chromosome include increase in nucleosome lability, enrichment for H4K16 acetylation and JIL-1 kinase, and depletion of linker histone H1 on active X-linked genes. Our finding serves as a model to understand how chromatin and local sequence features are involved in the selection of functional protein binding sites in the genome.
Publication Title
Sequence-specific targeting of dosage compensation in Drosophila favors an active chromatin context.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
- IlluminaHiSeq2000
Description
SMARCB1 (SNF5/INI1/BAF47), a core subunit of the SWI/SNF (BAF) chromatin remodeling complex, is inactivated in nearly all pediatric rhabdoid tumors. These aggressive cancers are among the most genomically stable, suggesting an epigenetic mechanism by which SMARCB1 loss drives transformation. Here, we show that despite indistinguishable mutational landscapes, human RTs show distinct enhancer H3K27ac signatures, which reveal remnants of differentiation programs. We show that SMARCB1 is required for the integrity of SWI/SNF complexes and that its loss alters enhancer targeting markedly impairing SWI/SNF binding to typical enhancers, particularly those required for differentiation, while maintaining SWI/SNF binding at super-enhancers. We show that these retained super-enhancers are essential for rhabdoid tumor survival, including some that are shared across all subtypes, such as SPRY1, and other lineage-specific super-enhancers like SOX2 in brain-derived RTs. Taken together, our findings reveal a novel chromatin-based epigenetic mechanism underlying the tumor suppressive activity of SMARCB1. Overall design: RNA-seq for three primary Rhabdoid tumor samples
Publication Title
SMARCB1-mediated SWI/SNF complex function is essential for enhancer regulation.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 3 Downloadable Samples
- Illumina Genome Analyzer II
Description
MSL (Male-specific lethal) complex increases transcription on the single X chromosome of Drosophila males in order to equalize expression of X-linked genes between males (XY) and females (XX). The increase in transcript levels correlates with MSL- dependent acetylation of histone H4 at K16 within the bodies of active genes, but identification of the transcriptional step affected has not been possible. In this study, we use global run-on sequencing (GRO-seq) to examine the specific effect of MSL complex on RNA Polymerase II (RNAP II) on a genome-wide level. Results indicate that MSL complex enhances transcription by facilitating the progression of RNAP II across the bodies of active X-linked genes. Improving transcriptional output downstream of typical gene-specific control may explain how dosage compensation can be imposed on the diverse set of genes along an entire chromosome. Overall design: Global Run-On Sequencing (GRO-Seq) reads, i.e., RNA-Seq of nascent RNA transcripts, from D. Melanogaster SL2 cells. Two biological replicates were analyzed.
Publication Title
Comprehensive analysis of the chromatin landscape in Drosophila melanogaster.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Lymph node metastasis is a poor prognosis indicator in esophageal cancer. Although tumor spreading currently forms the main basis for therapy selection, the molecular mechanisms underlying the metastatic pathway remain insufficiently understood. Several studies aimed to investigate these mechanisms but focused mainly on regulatory patterns in the tumors themselves and/or the invaded lymph nodes. To date no study has yet investigated the potential changes on transcription level, which take place within the yet non-invaded niche. Here we provide a comprehensive description of these regulations in patients. In this study the transcriptomic profiles of regional lymph nodes were determined for two patient groups: patients classified as pN1 (metastasis) or pN0 (no metastasis) respectively. All investigated lymph nodes, also those from pN1 patients, were still free of metastasis. The gene expression data was obtained via microarray analysis. Top candidates were validated via PCR and immunohistochemistry. The results show that regional lymph nodes of pN1 patients differ decisively from those of pN0 patients even before metastasis has taken place. In the pN0 group distinct immune response patterns were observed. In contrast, lymph nodes of the pN1 group exhibited a clear profile of reduced immune response and reduced proliferation, but increased apoptosis, enhanced hypoplasia and morphological conversion processes. DKK1 was the most significant gene associated with the molecular mechanisms taking place in lymph nodes of patients suffering from metastasis (pN1). We assume that the two molecular profiles observed constitute two different stages of a progressive disease. Finally we suggest that DKK1 might play an important role within the mechanisms leading to lymph node metastasis.
Publication Title
Molecular changes in pre-metastatic lymph nodes of esophageal cancer patients.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
It is unclear how nanosecond electrical pulses affect gene expression.
Publication Title
Evaluation of the Genetic Response of U937 and Jurkat Cells to 10-Nanosecond Electrical Pulses (nsEP).
Sample Metadata Fields
Specimen part, Cell line
View Samples