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Published on: May 30, 2012
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The Paf1 complex positively regulates enhancer activity in mouse embryonic stem cells
Li Ding1, Maciej Paszkowski-Rogacz1, Jovan Mircetic1,2
1Medical Systems Biology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Life Science Alliance
|December 30, 2020
Summary
The RNA polymerase II associated factor 1 complex (Paf1C) enhances gene expression by regulating super enhancers in mouse stem cells. This finding is crucial for maintaining stem cell self-renewal and understanding gene regulation.
Area of Science:
- Molecular Biology
- Gene Regulation
- Stem Cell Biology
Background:
- RNA polymerase II (RNAPII) associated factor 1 complex (Paf1C) influences RNAPII pausing and elongation.
- The precise role of Paf1C in regulating RNAPII pause release is complex and context-dependent, with conflicting models proposed, especially in cancer cells.
Purpose of the Study:
- To investigate the role of Paf1C in enhancer activity and gene regulation in mouse embryonic stem cells.
- To determine the functional significance of Paf1C occupancy at super enhancers.
Main Methods:
- Analysis of Paf1C occupancy at enhancers using ChIP-seq.
- Assessment of enhancer activity and gene expression following Paf1C depletion.
- Evaluation of RNAPII Ser2 phosphorylation levels.
Main Results:
- Paf1C positively regulates enhancer activity, particularly at super enhancers, in mouse embryonic stem cells.
- Paf1C occupancy strongly correlates with enhancer activity strength.
- Depletion of Paf1C reduces the expression of enhancer-regulated genes and impacts RNAPII Ser2 phosphorylation.
Conclusions:
- Paf1C plays a critical role in positively regulating pluripotency enhancer activity.
- Paf1C is essential for maintaining mouse embryonic stem cell self-renewal through its function at enhancers.
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