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Epigenetic Regulation of Cardiac Differentiation of Embryonic Stem Cells and Tissues
Published on: June 3, 2016
E2F4 regulates transcriptional activation in mouse embryonic stem cells independently of the RB family
Jenny Hsu1,2, Julia Arand1,2, Andrea Chaikovsky1,2
1Department of Pediatrics, 300 Pasteur Drive, Stanford University, Stanford, CA, 94305, USA.
Abstract:
E2F transcription factors are central regulators of cell division and cell fate decisions. E2F4 often represents the predominant E2F activity in cells. E2F4 is a transcriptional repressor implicated in cell cycle arrest and whose repressive activity depends on its interaction with members of the RB family. Here we show that E2F4 is important for the proliferation and the survival of mouse embryonic stem cells. In these cells, E2F4 acts in part as a transcriptional activator that promotes the expression of cell cycle genes. This role for E2F4 is independent of the RB family. Furthermore, E2F4 functionally interacts with chromatin regulators associated with gene activation and we observed decreased histone acetylation at the promoters of cell cycle genes and E2F targets upon loss of E2F4 in RB family-mutant cells. Taken together, our findings uncover a non-canonical role for E2F4 that provide insights into the biology of rapidly dividing cells.
Insights
E2F4 (E2F transcription factor 4) promotes mouse embryonic stem cell proliferation and survival by activating cell cycle genes, independent of RB family interactions. This reveals a novel role for E2F4 in rapidly dividing cells.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- E2F transcription factors regulate cell division and cell fate.
- E2F4 is typically a transcriptional repressor interacting with RB family proteins, associated with cell cycle arrest.
- E2F4 is the predominant E2F activity in many cell types.
Purpose of the Study:
- To investigate the role of E2F4 in mouse embryonic stem cell (mESC) proliferation and survival.
- To elucidate the mechanism by which E2F4 influences cell cycle gene expression in mESCs.
- To determine if E2F4's function in mESCs is dependent on the RB family.
Main Methods:
- Analysis of E2F4 function in mouse embryonic stem cells.
- Investigation of E2F4's interaction with RB family proteins.
- Assessment of E2F4's role in gene activation and chromatin modification (histone acetylation) at target gene promoters.
- Studies in RB family-mutant cells to assess E2F4 function.
Main Results:
- E2F4 is crucial for the proliferation and survival of mouse embryonic stem cells.
- In mESCs, E2F4 functions as a transcriptional activator, promoting cell cycle gene expression independently of the RB family.
- E2F4 interacts with chromatin regulators involved in gene activation.
- Loss of E2F4 leads to decreased histone acetylation at cell cycle gene promoters in RB family-mutant cells.
Conclusions:
- E2F4 plays a non-canonical role as a transcriptional activator in mouse embryonic stem cells.
- This function of E2F4 is essential for the proliferation and survival of rapidly dividing cells.
- E2F4's role in gene activation involves interaction with chromatin-modifying complexes.
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