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Cell signaling coordinates global Polycomb Repressive Complex 2 recruitment and gene expression in murine embryonic stem cells

Mohammad B. Aljazi, Yuen Gao, Yan Wu, George I. Mias, View ORCID ProfileJin He
doi: https://doi.org/10.1101/597674
Mohammad B. Aljazi
1Department of Biochemistry & Molecular Biology, College of Nature Sciences, Michigan State University, East Lansing, MI 48824
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Yuen Gao
1Department of Biochemistry & Molecular Biology, College of Nature Sciences, Michigan State University, East Lansing, MI 48824
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Yan Wu
1Department of Biochemistry & Molecular Biology, College of Nature Sciences, Michigan State University, East Lansing, MI 48824
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George I. Mias
1Department of Biochemistry & Molecular Biology, College of Nature Sciences, Michigan State University, East Lansing, MI 48824
2Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI 48824
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Jin He
1Department of Biochemistry & Molecular Biology, College of Nature Sciences, Michigan State University, East Lansing, MI 48824
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  • ORCID record for Jin He
  • For correspondence: hejin1@msu.edu
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Summary

The recruitment of Polycomb repressive complex 2 (PRC2) to gene promoters is critical for its function in repressing gene expression in murine embryonic stem cells (mESCs). However, previous studies have demonstrated although the expression of early lineage-specific genes is largely repressed, the genome-wide PRC2 occupancy is unexpectedly reduced in naïve mESCs. In this study, we provide evidence to show the FGF/ERK signaling determines the global PRC2 occupancy through regulating the expression of PRC2-recruting factor JARID2 in naïve mESCs. At the transcriptional level, the de-repression of bivalent genes is predominantly determined by the presence of cell signaling-associated transcription factors but not the status of PRC2 occupancy at gene promoters. Hence, this study not only reveals a key molecular mechanism by which the FGF/ERK signaling in regulating the PRC2 occupancy in mESCs, but also elucidates a fundamental question regarding the functional roles of transcription factors and Polycomb-mediated epigenetic mechanisms in transcriptional regulation.

Footnotes

  • Original Figures 1, 2, 3, 4, 5 revised, Add new figures 3, 6, 7, 8.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted January 17, 2020.
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Cell signaling coordinates global Polycomb Repressive Complex 2 recruitment and gene expression in murine embryonic stem cells
Mohammad B. Aljazi, Yuen Gao, Yan Wu, George I. Mias, Jin He
bioRxiv 597674; doi: https://doi.org/10.1101/597674
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Cell signaling coordinates global Polycomb Repressive Complex 2 recruitment and gene expression in murine embryonic stem cells
Mohammad B. Aljazi, Yuen Gao, Yan Wu, George I. Mias, Jin He
bioRxiv 597674; doi: https://doi.org/10.1101/597674

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