1. Parallel PRC2/cPRC1 and vPRC1 pathways silence lineage-specific genes and maintain self-renewal in mouse embryonic stem cells.
- Author
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Zepeda-Martinez JA, Pribitzer C, Wang J, Bsteh D, Golumbeanu S, Zhao Q, Burkard TR, Reichholf B, Rhie SK, Jude J, Moussa HF, Zuber J, and Bell O
- Subjects
- Animals, Gene Silencing, Mice, Models, Biological, Cell Differentiation genetics, Cell Lineage genetics, Cell Self Renewal genetics, Gene Expression Regulation, Developmental, Mouse Embryonic Stem Cells cytology, Mouse Embryonic Stem Cells metabolism, Polycomb Repressive Complex 1 metabolism, Polycomb Repressive Complex 2 metabolism
- Abstract
The transcriptional repressors Polycomb repressive complex 1 (PRC1) and PRC2 are required to maintain cell fate during embryonic development. PRC1 and PRC2 catalyze distinct histone modifications, establishing repressive chromatin at shared targets. How PRC1, which consists of canonical PRC1 (cPRC1) and variant PRC1 (vPRC1) complexes, and PRC2 cooperate to silence genes and support mouse embryonic stem cell (mESC) self-renewal is unclear. Using combinatorial genetic perturbations, we show that independent pathways of cPRC1 and vPRC1 are responsible for maintenance of H2A monoubiquitylation and silencing of shared target genes. Individual loss of PRC2-dependent cPRC1 or PRC2-independent vPRC1 disrupts only one pathway and does not impair mESC self-renewal capacity. However, loss of both pathways leads to mESC differentiation and activation of a subset of lineage-specific genes co-occupied by relatively high levels of PRC1/PRC2. Thus, parallel pathways explain the differential requirements for PRC1 and PRC2 and provide robust silencing of lineage-specific genes., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)
- Published
- 2020
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