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Myc binds the pluripotency factor Utf1 through the basic-helix-loop-helix leucine zipper domain
Agnieszka I Laskowski1, Paul S Knoepfler
1Department of Cell Biology and Human Anatomy, University of California Davis School of Medicine, Sacramento, CA 95817, USA.
Biochemical and Biophysical Research Communications
|May 14, 2013
Summary
We identified Undifferentiated embryonic cell transcription factor 1 (Utf1) as a novel Myc binding protein in mouse embryonic stem cells (mESCs). Utf1 plays a key role in maintaining pluripotency and self-renewal, potentially redundant with Myc.
Area of Science:
- Stem Cell Biology
- Molecular Biology
- Epigenetics
Background:
- Myc is crucial for maintaining pluripotency and self-renewal in mouse embryonic stem cells (mESCs).
- Identifying novel Myc interactors is essential for understanding its regulatory mechanisms in stem cells.
Purpose of the Study:
- To identify novel Myc-interacting proteins in mESCs using mass spectrometry.
- To characterize the interaction between Myc and its novel interactor, Undifferentiated embryonic cell transcription factor 1 (Utf1).
Main Methods:
- Mass spectrometry-based screening to identify Myc interactors in mESCs.
- Co-immunoprecipitation and Western blotting to confirm direct interaction between Myc and Utf1.
- Functional assays to assess the role of Utf1 in pluripotency and self-renewal.
- Analysis of shared target genes between Myc and Utf1.
- Mapping of interaction domains between N-Myc and Utf1.
Main Results:
- Utf1 was identified as a novel Myc-binding protein in mESCs.
- Myc and Utf1 directly interact.
- Utf1 is essential for maintaining pluripotency and self-renewal in mESCs.
- Utf1 can efficiently substitute for c-Myc in induced pluripotent stem cell (iPSC) generation.
- Myc and Utf1 share target genes, suggesting functional redundancy.
- Specific regions of Utf1 and N-Myc were identified as necessary for their direct interaction.
Conclusions:
- Utf1 is a novel, direct interactor of Myc in mESCs with a critical role in maintaining pluripotency and self-renewal.
- Utf1 exhibits functional redundancy with Myc and can substitute for c-Myc in iPSC generation.
- The findings reveal a new layer of regulation in stem cell maintenance involving the Myc-Utf1 complex.
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