Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing Other
Summary
Pluripotency is the ability of an embryonic stem (ES) cell to differentiate into all the different cell lineages of a mature organism. Naïve and primed pluripotent ES cells in vitro correspond to the pre- and post-implantation populations in the embryo, and they are developmentally linked to each other via progression through a ‘formative’ transition state where naïve ES cells mature in response to inductive cues prior to becoming specified towards certain cell fates. Studying the formative state is thus crucial for understanding the mechanisms of multi-lineage decision-making. Here we show that in the formative state there is a profound reorganisation of 3D genome structure, where genes whose expression levels are changing become located in multi-way chromatin hubs and highly intermingled regions of the genome. Our results suggest that the reorganisation of 3D genome structure is driven by changes in DNA methylation and Polycomb-mediated heterochromatin formation, which is accompanied by a global increase in transcriptional bursting, leading to a reconfiguration of enhancer-promoter interactions – consistent with changes in the epigenome priming promoters for lineage specific gene expression.
Overall design
ChIP-seq, single-cell RNA-seq and single-cell and population Hi-C in haploid and diploid mouse embryonic stem cells
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