This SuperSeries is composed of the SubSeries listed below.
Methyl-CpG-binding protein MBD2 plays a key role in maintenance and spread of DNA methylation at CpG islands and shores in cancer.
Cell line
View SamplesCancer is characterised by DNA hypermethylation and gene silencing of CpG island-associated promoters, including tumour suppressor genes The methyl-CpG-binding domain (MBD) family of proteins bind to methylated DNA and can aid in the meditation of gene silencing by interaction with histone deacetylases and histone methyltransferases. However the mechanisms responsible for eliciting CpG island hypermethylation in cancer, and the potential role that MBD may proteins play in modulation of the methylome remain unclear. Our previous work demonstrated that MBD2 preferentially binds to the hypermethylated GSTP1 promoter CpG island in prostate cancer cells. Here, we use functional genetic approaches to investigate if MBD2 plays an active role in promoting DNA methylation. First, we show that loss of MBD2 results in inhibition of both maintenance and spread of de novo methylation of a transfected construct containing the GSTP1 promoter CpG island in prostate cancer cells and Mbd2-/- mouse fibroblasts. De novo methylation was rescued by transient expression of Mbd2 in Mbd2-/- cells. Second, we show that MBD2 depletion triggers significant hypomethylation genome-wide in prostate cancer cells with concomitant loss of MBD2 binding at promoter and enhancer regulatory regions. Finally, CpG islands and shores that become hypomethylated after MBD2 depletion in LNCaP cancer cells show significant hypermethylation in clinical prostate cancer, highlighting a potential active role of MBD2 in promoting cancer specific hypermethylation. Importantly, co-immunoprecipiation of MBD2 reveals that MBD2 associates with DNA methyltransferase (DNMT) enzymes 1 and 3A. Together our results demonstrate that MBD2 plays a critical role in rewriting the cancer methylome at specific regulatory regions.
Methyl-CpG-binding protein MBD2 plays a key role in maintenance and spread of DNA methylation at CpG islands and shores in cancer.
Cell line
View SamplesStrand-specific RNA sequencing was done on a normal and a cancer cell line to examine how isoforms are used differently between these two states. Overall design: One PrEC sample, a normal cell line. One LNCaP sample, a cancer cell line.
Regional activation of the cancer genome by long-range epigenetic remodeling.
Cell line, Subject
View SamplesCapped analysis of gene expression (CAGE) sequencing was done on a normal and a cancer cell line to examine how promoter usage changes between these two states. Overall design: One PrEC sample, a normal cell line. One LNCaP sample, a cancer cell line.
Regional activation of the cancer genome by long-range epigenetic remodeling.
Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Consolidation of the cancer genome into domains of repressive chromatin by long-range epigenetic silencing (LRES) reduces transcriptional plasticity.
Specimen part, Cell line
View SamplesA three-dimensional chromatin state underpins the structural and functional basis of the genome by bringing regulatory elements and genes into close spatial proximity to ensure proper, cell-type specific gene expression profiles. Here, we perform HiC chromosome conformation, ChIP-seq and RNA-seq to investigate how the three-dimensional organization of the cancer genome is disrupted in the context of epigenetic remodelling and atypical gene expression programs. Overall design: Hi-C, ChIP-seq and RNA-seq were conducted in three human prostate cell lines: normal prostate epithelial cells (PrEC) and prostate cancer cells (PC3 and LNCaP).
Three-dimensional disorganization of the cancer genome occurs coincident with long-range genetic and epigenetic alterations.
No sample metadata fields
View SamplesTo identify genomic regions which display concordant gene expression in prostate cancer, we performed expression profiling of normal prostate epithelial cells (PrEC) and the prostate cancer cell line LNCaP.
Consolidation of the cancer genome into domains of repressive chromatin by long-range epigenetic silencing (LRES) reduces transcriptional plasticity.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Enduring epigenetic landmarks define the cancer microenvironment.
Sex, Specimen part, Subject
View SamplesTo understand the molecular differences between adipocytes and their contribution to cell-type specific function, we comprehensively characterised the transcriptomes and DNA methylomes using WGBS of isolated adipocytes from the SAT and VAT from normal weight individuals Overall design: WGBS, RNA-seq, and microarrays were used to study epigenetics and transcriptomics human cancer isolated subcutaneous (abdominal - SA) and vieceral (omental - VA) adipocyte, peripheral blood leukocytes (PBL) and visceral adipose tissue (VAT).
Methylome and transcriptome maps of human visceral and subcutaneous adipocytes reveal key epigenetic differences at developmental genes.
Sex, Specimen part, Subject
View SamplesCancer Associated Fibroblasts (CAFs) play an active role in tumourigenesis. It is unknown how the permanent phenotypic changes in CAFs are encoded at the molecular level. Here we use whole genome sequencing and microarray analysis to interrogate the epigenome, transcriptome and genome of patient-matched CAF and non-malignant prostate fibroblast (NPF) cells.
Enduring epigenetic landmarks define the cancer microenvironment.
Sex, Specimen part, Subject
View Samples