Project description:Chromatin modifications provide additional context-dependence for DNA sequence-based gene regulation. Binding sites of the transcription factor (TF) and important tumour suppressor p53 are unusually diverse with regards to their chromatin accessibility and histone modifications, suggesting different modes of binding. Here, we show that the ability of p53 to open chromatin and activate its target genes is locally restricted by its cofactor Trim24. The histone-binding domains of Trim24 limits the role of p53 at closed chromatin but not at accessible chromatin where Trim24 is blocked by histone 3 methylation at lysine 4. In turn, p53 regulates gene expression as a function of the naïve chromatin state prior to activation. These findings establish a novel mode of gene regulation by p53 in closed chromatin and illustrate how histone modification sensing cofactors can bridge local chromatin state and TF potency.
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
Project description:In this study, we characterize the fusion protein produced by the EPC1-PHF1 translocation in Low Grade Endometrial Stromal Sarcoma (LG-ESS) and Ossifying FibroMyxoid Tumors (OFMT). We express the fusion protein and necessary controls in K562 Cells. The fusion protein assembles a mega-complex harboring both NuA4/TIP60 and PRC2 subunits and enzymatic activities and leads to mislocalization of chromatin marks in the genome, linked to aberrant gene expression.