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Polycomb enables primitive endoderm lineage priming in embryonic stem cells.
Robert S Illingworth1, Jurriaan J Hölzenspies2,3, Fabian V Roske2
1MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
Elife
|October 11, 2016
Summary
Mouse embryonic stem cells (ESCs) exhibit lineage priming, a process driven by polycomb activities and altered transcription. This research reveals how H3K27me3 modification influences cell fate decisions before definitive lineage commitment.
Area of Science:
- Developmental Biology
- Stem Cell Biology
- Epigenetics
Background:
- Mouse embryonic stem cells (ESCs) possess precursors for epiblast (Epi) and primitive endoderm (PrEn) lineages.
- These precursor populations can interconvert in vitro, a process known as lineage priming.
Purpose of the Study:
- To investigate the role of polycomb activities and transcriptional changes in ESC lineage priming.
- To determine the specific involvement of H3K27me3 modification in regulating lineage commitment.
Main Methods:
- Analysis of intragenic and promoter-proximal H3K27me3 levels in ESCs.
- Depletion of H3K27me3 modification to assess its impact on differentiation and gene expression.
- Monitoring transcriptional changes associated with lineage priming.
Main Results:
- Intragenic H3K27me3 levels anti-correlated with transcriptional changes, independent of gene identity.
- Promoter-proximal H3K27me3 was elevated for PrEn priming genes.
- H3K27me3 depletion enhanced PrEn priming during differentiation but minimally affected self-renewing ESCs.
Conclusions:
- Polycomb activity, specifically H3K27me3, dynamically regulates transcription during lineage priming.
- H3K27me3 plays a role in stalling lineage commitment, allowing ESCs to maintain plasticity.
- This epigenetic mechanism enables cells to explore alternative cell fate choices before irreversible differentiation.
Keywords:
Embryonic Stem CellsH3K27me3HeterogeneityLineage PrimingPolycombTranscriptionchromosomesdevelopmental biologygenesmousestem cellsMore Related Videos
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