Human engeneered skin carrying GFP positive melanoma cells was transplanted in immunocompromised rats.
low neurotrophin receptor CD271 regulates phenotype switching in melanoma.
Specimen part, Time
View SamplesIncreased activity of the epigenetic modifier EZH2 has been associated with different cancers. However, evidence for a functional role of EZH2 in tumourigenesis in vivo remains poor, in particular in metastasising solid cancers. Here we reveal central roles of EZH2 in promoting growth and metastasis of cutaneous melanoma. In a melanoma mouse model, conditional Ezh2 ablation as much as treatment with the preclinical Ezh2 inhibitor GSK503 stabilises the disease through inhibition of growth and virtually abolishes metastases formation without affecting normal melanocyte biology. Comparably, in human melanoma cells, EZH2 inactivation impairs proliferation and invasiveness, accompanied by re-expression of tumour suppressors connected to increased patient survival. These EZH2 target genes suppress melanoma growth and prevent EMT / metastasis in vivo revealing the dual function of EZH2 in promoting tumour progression. Thus, EZH2-mediated epigenetic repression is highly relevant especially during advanced melanomagenesis, which makes EZH2 a promising target for novel melanoma therapies.
The epigenetic modifier EZH2 controls melanoma growth and metastasis through silencing of distinct tumour suppressors.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Yin Yang 1 extends the Myc-related transcription factors network in embryonic stem cells.
Specimen part
View SamplesWe have determined the global gene expression upon loss of function of the Yy1 transcription factor in mouse embryonic stem cells
Yin Yang 1 extends the Myc-related transcription factors network in embryonic stem cells.
Specimen part
View SamplesThis experiment was designed to indentify RNAs making direct contact with EZH2 in mouse embryonic stem cells Overall design: E14 with an integrated transgene encoding HA-EZH2 were pulsed with 4-SU, irradiated with UV, and subjected to HA immunoprecipitation.
PRC2 binds active promoters and contacts nascent RNAs in embryonic stem cells.
Cell line, Subject
View SamplesThis experiment was designed to obtain the polyA+ transcriptome in E14 ESCs Overall design: PolyA+ RNA was extracted and purified from two separate clones of E14, which were treated as biological replicate
PRC2 binds active promoters and contacts nascent RNAs in embryonic stem cells.
Cell line, Subject
View SamplesThis experiment sought to determine the genome-wide interactome of CTCF in human cells. Overall design: PAR-CLIP seq for CTCF was performed in U2OS cells in 2 biological replicates
CTCF regulates the human p53 gene through direct interaction with its natural antisense transcript, Wrap53.
No sample metadata fields
View SamplesSFMBT1 is a poorly characterized mammalian MBT domain-containing protein homologous to Drosophila SFMBT, a Polycomb group protein involved in epigenetic regulation of gene expression. Here, we show that SFMBT1 regulates transcription in somatic cells and during spermatogenesis through the formation of a stable complex with LSD1 and CoREST. When bound to its gene targets, SFMBT1 recruits its associated proteins and causes chromatin compaction and transcriptional repression. SFMBT1, LSD1, and CoREST share a large fraction of target genes including those encoding replication-dependent histones. Simultaneous occupancy of histone genes by SFMBT1, LSD1, and CoREST is regulated during the cell cycle and correlates with the loss of RNA polymerase II at these promoters during G2, M, and G1. The interplay between the repressive SFMBT1–LSD1–CoREST complex and RNA polymerase II contributes to the timely transcriptional regulation of histone genes in human cells. SFMBT1, LSD1, and CoREST also form a stable complex in germ cells and their chromatin binding activity is regulated during spermatogenesis. Overall design: RNA-seq in HeLaS3 cells ctrl compared to triple knockdown for SFMBT1, CoREST, and LSD1
SFMBT1 functions with LSD1 to regulate expression of canonical histone genes and chromatin-related factors.
Cell line, Treatment
View SamplesThe activity of enhancers and promoters fine-tunes the transcriptional program of mammalian cells through the recruitment and interplay between cell type-specific and ubiquitous transcription factors. Despite their key role in modulating transcription, the identification of enhancers is challenged by their limited sequence conservation and highly variable distance from target genes. Although enhancers are characterised by the strong enrichment of mono-methylation at lysine 4 of histone H3, mirrored by low tri-methylation at the same residue, a comprehensive list of enhancers-associated histone post-translational modifications (PTMs) is still lacking. We undertook a proteomics investigation, based on chromatin immunoprecipitation combined with mass spectrometry (MS), to identify histone marks specifically associated to cis-regulatory elements in macrophages, focusing on enhancers. We also profiled their plasticity during the transcriptional activation induced by an inflammatory stimulus. The proteomic analysis suggested novel PTM associations, which were validated by analysis of ChIP- and RNA-seq data, whose intersection revealed the existence of novel sub-populations of enhancers marked by specific signatures: the dual mark H3K4me1/K36me2 labels transcription at enhancers, whereas H3K4me1/K36me3 and H3K4me1/K79me2 tag distinct intronic enhancers. While demonstrating that analyzing restricted genomic regions can disclose the combinatorial language of histone modifications, this study highlights the potential of MS-based proteomics in addressing fundamental questions in epigenetics. Overall design: Total RNA was extracted from 5x10^6 untreated RAW 264.7 cells using RNAeasy kit (Qiagen). Libraries were then prepared using TruSeq RNA sample preparation Kit (Illumina) after depleting ribosomal RNA
Chromatin proteomics reveals novel combinatorial histone modification signatures that mark distinct subpopulations of macrophage enhancers.
Specimen part, Cell line, Treatment, Subject
View SamplesTumor tissue heterogeneity is a well known feature of several solid tumors. Neuroblastic Tumors (NTs) is a group of paediatric cancers with a great tissue heterogeneity. Most of NTs are composed of undifferentiated, poorly differentiated or differentiating neuroblastic (Nb) cells with very few or absent Schwannian stromal (SS) cells: these tumors are grouped as Neuroblastoma (Schwannian stroma-poor). The remaining NTs are composed of abundant SS cells and classified as Ganglioneuroblastoma (Schwannian stroma-rich) intermixed or nodular and Ganglioneuroma. The importance to understand Nb and SS gene signatures in NTs, is to clarify the complex network mechanism of tumor growth and progression. In order to identify the Nb and SS cells gene signatures, we analyzed the gene expression profiling of 19 cases of neuroblastic tumors: 10 stroma poor (NTs-SP) and 9 stroma rich (NTs-SR), by high density oligonucleotide microarrays. Moreover, the analysis was performed in parallel on both whole and laser microdissected tumor samples: from 4 of 19 cases, was isolated different areas all composed of pure cellular populations.
Identification of low intratumoral gene expression heterogeneity in neuroblastic tumors by genome-wide expression analysis and game theory.
No sample metadata fields
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