Projects per year
Abstract
Polycomb group (PcG) proteins silence gene expression by chemically and physically modifying chromatin. A subset of PcG target loci are compacted and cluster in the nucleus; a conformation which is thought to contribute to gene silencing. However, how these interactions influence gross nuclear organisation and their relationship with transcription remains poorly understood. Here we examine the role of Polycomb Repressive Complex 1 (PRC1) in shaping 3D genome organization in mouse embryonic stem cells (mESCs). Using a combination of imaging and Hi-C analyses we show that PRC1-mediated long-range interactions are independent of CTCF and can bridge sites at a megabase scale. Impairment of PRC1 enzymatic activity does not directly disrupt these interactions. We demonstrate that PcG targets coalesce in vivo, and that developmentally induced expression of one of the target loci disrupts this spatial arrangement. Finally, we show that transcriptional activation and the loss
of PRC1-mediated interactions are separable events. These findings provide important insights into the function of PRC1, whilst highlighting the complexity of this regulatory system.
of PRC1-mediated interactions are separable events. These findings provide important insights into the function of PRC1, whilst highlighting the complexity of this regulatory system.
Original language | English |
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Pages (from-to) | 931-949 |
Journal | Genes & Development |
Volume | 34 |
Issue number | 13-14 |
Early online date | 21 May 2020 |
DOIs | |
Publication status | Published - 1 Jul 2020 |
Keywords
- polycomb
- topologically associating domains (TADs)
- gene repression
- nuclear organization
- embryonic stem cells
- gene regulation
- epigenetics
- histone modifications
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Cell-Specific PRC1 Accessory Proteins and the Regulation of Mammalian Neurodevelopment
1/04/19 → 31/03/24
Project: Research
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MC_UU_00007/2 The role of spatial nuclear organisation in genome function
1/04/18 → 1/04/23
Project: Research
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Integrating developmental pathways and chromatin structure during lineage specifcation
1/10/11 → 31/07/13
Project: Research
Profiles
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Robert Illingworth
- Deanery of Clinical Sciences - Senior Research Fellow / Group Leader
- Edinburgh Neuroscience
- Centre for Regenerative Medicine
Person: Academic: Research Active , Academic: Research Active (Research Assistant)