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Published on: May 30, 2012
Cell Signaling Coordinates Global PRC2 Recruitment and Developmental Gene Expression in Murine Embryonic Stem Cells
Mohammad B Aljazi1, Yuen Gao1, Yan Wu1
1Department of Biochemistry and Molecular Biology, College of Natural Science, Michigan State University, East Lansing, MI 48824, USA.
Abstract:
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 that although the expression of early lineage-specific genes is largely repressed, the genome-wide PRC2 occupancy is unexpectedly reduced in naive mESCs. In this study, we provide evidence that fibroblast growth factor/extracellular signal-regulated kinase signaling determines the global PRC2 occupancy through regulating the expression of PRC2-recruiting factor JARID2 in naive 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 cell signaling regulates the PRC2 occupancy in mESCs but also elucidates the functional roles of transcription factors and Polycomb-mediated epigenetic mechanisms in transcriptional regulation.
Insights
Fibroblast growth factor/extracellular signal-regulated kinase signaling regulates Polycomb repressive complex 2 (PRC2) occupancy in mouse embryonic stem cells (mESCs) by controlling JARID2 expression. Cell signaling, not PRC2 levels, dictates bivalent gene de-repression.
Area of Science:
- Epigenetics
- Stem Cell Biology
- Molecular Biology
Background:
- Polycomb repressive complex 2 (PRC2) is crucial for gene silencing in mouse embryonic stem cells (mESCs).
- Genome-wide PRC2 occupancy is paradoxically reduced in naive mESCs despite repression of key developmental genes.
Purpose of the Study:
- To investigate the molecular mechanisms linking cell signaling to PRC2 occupancy in naive mESCs.
- To understand the roles of transcription factors and epigenetic mechanisms in regulating gene expression during early lineage commitment.
Main Methods:
- Analysis of PRC2 occupancy and gene expression in mESCs under varying signaling conditions.
- Investigation of the role of JARID2 as a PRC2-recruiting factor.
- Assessment of the impact of cell signaling-associated transcription factors on bivalent gene regulation.
Main Results:
- Fibroblast growth factor/extracellular signal-regulated kinase (FGF/ERK) signaling directly influences global PRC2 occupancy in mESCs.
- FGF/ERK signaling regulates PRC2 occupancy by modulating the expression of JARID2.
- De-repression of bivalent genes is primarily driven by cell signaling transcription factors, independent of PRC2 promoter occupancy.
Conclusions:
- Cell signaling pathways play a critical role in modulating epigenetic states by regulating PRC2 recruitment in mESCs.
- Transcriptional regulation in early development involves a complex interplay between cell signaling and Polycomb-mediated epigenetic control.
- JARID2 acts as a key mediator connecting FGF/ERK signaling to PRC2 function in naive stem cells.
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