RNA polymerase II primes Polycomb‐repressed developmental genes throughout terminal neuronal differentiation
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 rep...
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| Format: | Article |
| Language: | English |
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Springer Nature
2017-10-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.15252/msb.20177754 |
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| _version_ | 1849760985986891776 |
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| author | Carmelo Ferrai Elena Torlai Triglia Jessica R Risner‐Janiczek Tiago Rito Owen JL Rackham Inês de Santiago Alexander Kukalev Mario Nicodemi Altuna Akalin Meng Li Mark A Ungless Ana Pombo |
| author_facet | Carmelo Ferrai Elena Torlai Triglia Jessica R Risner‐Janiczek Tiago Rito Owen JL Rackham Inês de Santiago Alexander Kukalev Mario Nicodemi Altuna Akalin Meng Li Mark A Ungless Ana Pombo |
| author_sort | Carmelo Ferrai |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ae912ea041524599bb072c1b35d0faa4 |
| institution | DOAJ |
| issn | 1744-4292 |
| language | English |
| publishDate | 2017-10-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-ae912ea041524599bb072c1b35d0faa42025-08-20T03:06:10ZengSpringer NatureMolecular Systems Biology1744-42922017-10-01131012510.15252/msb.20177754RNA polymerase II primes Polycomb‐repressed developmental genes throughout terminal neuronal differentiationCarmelo Ferrai0Elena Torlai Triglia1Jessica R Risner‐Janiczek2Tiago Rito3Owen JL Rackham4Inês de Santiago5Alexander Kukalev6Mario Nicodemi7Altuna Akalin8Meng Li9Mark A Ungless10Ana Pombo11Epigenetic Regulation and Chromatin Architecture, Max Delbrück Center for Molecular MedicineEpigenetic Regulation and Chromatin Architecture, Max Delbrück Center for Molecular MedicineInstitute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College LondonEpigenetic Regulation and Chromatin Architecture, Max Delbrück Center for Molecular MedicineDuke‐NUS Medical SchoolGenome Function, MRC London Institute of Medical Sciences (previously MRC Clinical Sciences Centre)Epigenetic Regulation and Chromatin Architecture, Max Delbrück Center for Molecular MedicineDipartimento di Fisica, Università di Napoli Federico II and INFN Napoli, Complesso Universitario di Monte Sant'AngeloScientific Bioinformatics Platform, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular MedicineInstitute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College LondonInstitute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College LondonEpigenetic Regulation and Chromatin Architecture, Max Delbrück Center for Molecular MedicineAbstract 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.https://doi.org/10.15252/msb.20177754cell plasticitychromatin bivalencygene regulationRNA polymerase IItranscriptional poising |
| spellingShingle | Carmelo Ferrai Elena Torlai Triglia Jessica R Risner‐Janiczek Tiago Rito Owen JL Rackham Inês de Santiago Alexander Kukalev Mario Nicodemi Altuna Akalin Meng Li Mark A Ungless Ana Pombo RNA polymerase II primes Polycomb‐repressed developmental genes throughout terminal neuronal differentiation Molecular Systems Biology cell plasticity chromatin bivalency gene regulation RNA polymerase II transcriptional poising |
| title | RNA polymerase II primes Polycomb‐repressed developmental genes throughout terminal neuronal differentiation |
| title_full | RNA polymerase II primes Polycomb‐repressed developmental genes throughout terminal neuronal differentiation |
| title_fullStr | RNA polymerase II primes Polycomb‐repressed developmental genes throughout terminal neuronal differentiation |
| title_full_unstemmed | RNA polymerase II primes Polycomb‐repressed developmental genes throughout terminal neuronal differentiation |
| title_short | RNA polymerase II primes Polycomb‐repressed developmental genes throughout terminal neuronal differentiation |
| title_sort | rna polymerase ii primes polycomb repressed developmental genes throughout terminal neuronal differentiation |
| topic | cell plasticity chromatin bivalency gene regulation RNA polymerase II transcriptional poising |
| url | https://doi.org/10.15252/msb.20177754 |
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