Epigenetic and genome architecture dynamics from ES cells to terminal differentiation

March 10th 2017
Versione stampabile

Venue: Edificio Povo 2, via Sommarive nr. 9, Povo (Tn) - Room B105
 At 2:00 p.m.

  • Carmelo Ferrai - Berlin Institute for Medical Systems Biology (BIMSB), Max-Delbrück-Center for Molecular Medicin (MDC),  Berlin, Germany

Polycomb repression at developmentally regulated genes in mouse ES cells is associated with promoter co-occupancy of Polycomb repressor complexes and an unusual form of RNAPII. RNAPII at Polycomb targets is phosphorylated only on S5 residues of the CTD but not on S7 or S2 residues, which mark transcription at active genes. It remains unknown whether the Polycomb-repressed RNAPII state is specific of pluripotent cells or a more general feature of Polycomb repression. To answer this biological question we explored the epigenetic phenomena of the interplay between Polycomb repression, RNAPII occupancy and gene expression during terminally differentiating neurons. In order to study these chromatin dynamics we performed high-throughput mapping of H3K27me3, RNAPII-S5p and RNAPII-S7p occupancy and mRNA-seq expression throughout five stages of ESC differentiation to dopaminergic neurons. We find that many Polycomb targets maintain their RNAPII state when cells exit pluripotency to the different stages of maturity of dopaminergic neurons. We also identify novel targets of Polycomb and waves of transient downregulation of active genes that coincides with Polycomb repression. Importantly poised genes found in neurons are candidate master regulators for trans-differentiation.