Widespread chromatin accessibility at repetitive elements links embryonic stem cells with human cancer

Examination of chromatin accessibility in three human embryonic stem cell lines unexpectedly identified a stem cell signature consisting of widespread enrichment of repetitive elements (RE). Integrating genomic and biochemical approaches we found that RE in accessible chromatin are flanked by well positioned nucleosomes and distinct histone modifications, similar to that of other regulatory elements. Chromatin remodeling at repetitive elements during differentiation was associated with differential gene expression and developmental pathways. Remarkably, we found that the chromatin environment of a mesenchymally-derived cancer, Ewing Sarcoma, mimics that of bone-marrow-derived multipotent stromal cells creating a permissive environment for the central oncogene responsible for this cancer. Our data demonstrate that chromatin in stem cells is characterized by a unique signature consisting of an enrichment of repetitive elements that are associated with both differentiation and disease. Examination of FAIRE-seq, DNase-seq, MNase-seq, RNA-seq in human stem cells and differentiated cells. ----------------------------------- *Incomplete: No raw data provided for all bone marrow samples