GSE161531
DNA G-quadruplexes in human stem cells and during differentiation
The establishment of cell identity involves the activation of developmental gene expression programs and is underpinned by epigenetic factors including DNA methylation and histone modifications. G-quadruplex DNA secondary structures (G4) are genomic elements implicated in transcriptional regulation, genome instability and cancer. We reasoned that G4s might be central features that influence development. In human embryonic stem cells G4s are highly abundant and progressively lost during differentiation. They are prevalent in enhancers and promoters and their inheritance is linked to transcriptional stabilisation of key homeostasis genes and to transitions in the histone modification landscape. Interventional G4 stabilisation by a small molecule leads to developmental delay. Our findings suggest that G4s are epigenetic marks involved in stem cell pluripotency and differentiation. Overall design: DNA G-quadruplexes (G4-ChIP-seq), accessibility (ATAC-seq) and gene expression have been profiled in three stem cells:  H9 human embryonic stem cells (ESC), H9-derived cranial neural crest cells (CNCCs) and in H9-derived neural stem cells (NSC).  For G4-ChIP-seq 3 biological replicates have been performed, and each of those have been assessed by 3 technical replicates and 1 input library.Three biological replicates per cell type for ATAC-seq were performed. Furthermore, 5 biological replicates for ESC, 3 biological replicates for CNCC, 4 biological replicates for NSC were performed for RNA-seq.