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

Ferrai, Carmelo, Triglia, Elena Torlai, Risner-Janiczek, Jessica R., Rito, Tiago, Rackham, Owen J. L., Inês, de Santiago, Kukalev, Alexander, Nicodemi, Mario, Akalin, Altuna, Li, Meng ORCID: https://orcid.org/0000-0002-4803-4643, Ungless, Mark A. and Pombo, Ana 2017. RNA polymerase II primes Polycomb-repressed developmental genes throughout terminal neuronal differentiation. Molecular Systems Biology 13 (10) , 946. 10.15252/msb.20177754

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences Medicine Neuroscience and Mental Health Research Institute (NMHRI)
Additional Information:	This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Publisher:	Wiley
ISSN:	1744-4292
Date of First Compliant Deposit:	12 September 2017
Date of Acceptance:	11 September 2017
Last Modified:	05 May 2023 11:00
URI:	https://orca.cardiff.ac.uk/id/eprint/104550

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