Project description:The Wilms' tumour 1 transcription factor regulates epigenetic states via DNA methyltransferase 3A. The data consists of two Nimblegen promoter/CpG island microarrays hybridized with MCIP DNA immunoprecipitated from either a HEK293-derived cell line expressing a heterologous WT1 cDNA (W210) or a control cell line containing the expression vector (IP100), both hybridized against input DNA.
Project description:Epigenetic dysregulation is a universal feature of cancer that results in altered patterns of gene expression that drive malignancy. Brain tumors exhibit subtype-specific epigenetic alterations, however the molecular mechanisms responsible for these diverse epigenetic states remain unclear. Here we show that the developmental transcription factor Sox9 differentially regulates epigenomic states in high-grade glioma (HGG) and ependymoma (EPN). These contrasting roles for Sox9 correspond with protein interactions with histone deacetylating complexes in HGG, and association with the Rela oncofusion in EPN. Together, our studies demonstrate how epigenomic states are differentially regulated in distinct subtypes of brain tumors, while revealing divergent roles for Sox9 in HGG and EPN tumorigenesis.
Project description:Frequent long-range epigenetic silencing of protocadherin gene clusters on chromosome 5q31 in Wilms' tumour The data consists of five microarrays hybridized with methylated DNA immunoprecipitated from Wilms' tumours and from a normal foetal kidney control
Project description:We describe how the cancer-causing Epstein-Barr virus (EBV), a prototypic herpesvirus, alters proteome at viral replication forks prominently identifies chromatin modifying and transcriptional repression proteins. Specifically, to transition from transcription, the viral DNA polymerase processivity factor EA-D is SUMOylated by the transcriptional corepressor KAP1-TRIM28. KAP1 function is triggered by phosphorylation via the PI3K-related kinase ATM and the helicase RECQ5 at the transcription machinery. SUMO-EA-D recruits the histone loader CAF1 and the methyltransferase SETDB1 to silence the parental genome, prioritizing replication. Thus, DNA repair, epigenetic, and transcription-replication interference pathways orchestrate the handover from transcription to replication, a fundamental feature of DNA viruses
Project description:We have previously determined the insulin-like growth factor 1 receptor (IGF1R) to be amplified and overexpressed in Wilms tumour. In order to probe the efficacy and mechanisms of action of various inhibitors of the receptor, we have carried out expression profiling of Wilms tumour cells treated with 5x IC50 of the compounds PPP and NVP-AEW541 over a 24 hour time-course.
Project description:Protein arginine methylation is an important process, which regulates diverse cellular functions including cell proliferation, RNA stability, DNA repair and gene transcription. Based on literature search, protein arginine methyltransferase (PRMT) indeed plays important roles in colon cancer pathophysiology. The PRMT expression level is involved in colon cancer patient’s survival and has been suggested to be a prognostic marker in colon cancer patients. Recently, our group found a novel methylation on epidermal growth factor receptor (EGFR), which affected EGFR downstream signaling. investigators further observed the methylation event on EGFR not only regulated tumor growth in mouse xenograft model but also influenced cetuximab response in colon cancer cell lines. To further study the clinical correlation between EGFR methylation and cetuximab response, we propose to detect EGFR methylation level in paraffin embedded tissue samples from colorectal cancer patients with or without cetuximab treatment by IHC staining and analyze its correlation with cetuximab response. This study will provide an insight to the strategy of colorectal cancer therapy.
Project description:By rational engineering of the transcription factor SOX2, a key promoter of GBM malignancy, we generated a synthetic repressor named SOX2 Epigenetic Silencer (SES), which maintains the ability to bind to a large group of its original targets. Data from RNAseq, ATACseq, MeDIPseq, ChIPseq in GBM cells indicate that SES, through the KRAB and DNA methyltransferase 3A/L catalytic domains, epigenetically inhibits the SOX2 tumorigenic molecular network (rather than activating it as SOX2 does). This epigenetic long-term transcriptional silencing includes genes crucial for tumor maintenance and growth. Conversely, transcriptomic and epigenomic data show that SES is ineffective (thus not harmful) in healthy neural cells.
