Format

Send to

Choose Destination
Mol Syst Biol. 2017 Oct 16;13(10):946. doi: 10.15252/msb.20177754.

RNA polymerase II primes Polycomb-repressed developmental genes throughout terminal neuronal differentiation.

Author information

1
Epigenetic Regulation and Chromatin Architecture, Max Delbrück Center for Molecular Medicine, Berlin, Germany carmelo.ferrai@mdc-berlin.de mark.ungless@imperial.ac.uk ana.pombo@mdc-berlin.de.
2
Genome Function, MRC London Institute of Medical Sciences (previously MRC Clinical Sciences Centre), London, UK.
3
Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London, UK.
4
Epigenetic Regulation and Chromatin Architecture, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
5
Stem Cell Neurogenesis, MRC London Institute of Medical Sciences (previously MRC Clinical Sciences Centre), London, UK.
6
Neurophysiology Group, MRC London Institute of Medical Sciences (previously MRC Clinical Sciences Centre), London, UK.
7
Duke-NUS Medical School, Singapore, Singapore.
8
Dipartimento di Fisica, Università di Napoli Federico II and INFN Napoli, Complesso Universitario di Monte Sant'Angelo, Naples, Italy.
9
Scientific Bioinformatics Platform, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
10
Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London, UK carmelo.ferrai@mdc-berlin.de mark.ungless@imperial.ac.uk ana.pombo@mdc-berlin.de.
11
Institute for Biology, Humboldt-Universität zu Berlin, Berlin Germany.

Abstract

Polycomb repression in mouse embryonic stem cells (ESCs) is tightly associated with promoter co-occupancy of RNA polymerase II (RNAPII) which is thought to prime genes for activation during early development. However, it is unknown whether RNAPII poising is a general feature of Polycomb repression, or is lost during differentiation. Here, we map the genome-wide occupancy of RNAPII and Polycomb from pluripotent ESCs to non-dividing functional dopaminergic neurons. We find that poised RNAPII complexes are ubiquitously present at Polycomb-repressed genes at all stages of neuronal differentiation. We observe both loss and acquisition of RNAPII and Polycomb at specific groups of genes reflecting their silencing or activation. Strikingly, RNAPII remains poised at transcription factor genes which are silenced in neurons through Polycomb repression, and have major roles in specifying other, non-neuronal lineages. We conclude that RNAPII poising is intrinsically associated with Polycomb repression throughout differentiation. Our work suggests that the tight interplay between RNAPII poising and Polycomb repression not only instructs promoter state transitions, but also may enable promoter plasticity in differentiated cells.

KEYWORDS:

RNA polymerase II; cell plasticity; chromatin bivalency; gene regulation; transcriptional poising

PMID:
29038337
PMCID:
PMC5658700
DOI:
10.15252/msb.20177754
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center