Abstracts (poster) - Wissenschaft Online

Fabio Mohn, Michael Weber, Michael Rebhan, Tim Roloff, Jens Richter, Michael Stadler,
Miriam Bibel, Dirk Schübeler
Lineage-specific Polycomb targets and de novo DNA
methylation define restriction and potential of neuronal
progenitors
Reduction of cellular potency during development is thought to employ epigenetic
restriction. We have used a murine neuronal differentiation system that progresses from
embryonic stem cells to lineage-committed progenitors and further to postmitotic,
terminally differentiated neurons to identify genes targeted by two repressive epigenetic
pathways: DNA methylation and Polycomb-mediated methylation of histone H3
(H3K27me3).
We show that CpG-rich promoters are unmethylated in stem cells, yet several hundred
become DNA methylated in lineage-committed progenitor cells with no further
methylation during terminal differentiation. Targeted promoters control pluripotency and
germline-specific genes, suggesting a role for DNA methylation in stabilizing loss of
pluripotency.
Conversely, we detect acquisition and loss of H3K27me3 at novel targets at both
progenitor and terminal state. Surprisingly, neuron-specific genes that are poised to be
activated upon further terminal differentiation, become Polycomb targets in progenitor
cells. Moreover, the presence of H3K27me3 in stem cells primes for differentiationcoupled
DNA methylation, suggesting context-dependent crosstalk between Polycomb
and DNA methylation.
Our analysis illustrates that de novo DNA methylation and dynamic switches in Polycomb
targets cooperate to establish epigenetic states specific for restricting pluripotency and
defining the developmental potential of progenitor cells.
contact:
Fabio Mohn
Friedrich Miescher Institute for Biomedical Research
fabio.mohn@fmi.ch
Maulbeerstrasse 66
4058 Basel (Switzerland)
additional information
Address affiliation of Miriam Bibel and Jens Richter:
Novartis Institutes for Biomedical Research, Neurodegeneration Department, 4002 Basel,
Switzerland