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Cell fate conversion: a chromatin remodeling checkpoint revealed.
1Institute for Regenerative Medicine, Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, 9-131 SCTR, 3400 Civic Center Blvd., Philadelphia, PA 19104-5157, USA.
Cell Research
|April 1, 2017
Summary
Cell reprogramming triggers a chromatin remodeling checkpoint. This mechanism, involving the Baf60b complex and ATM-p53 pathway, causes cell death to prevent aberrant cell fate changes and cancer.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Cell reprogramming involves significant chromatin structure alterations.
- Aberrant cell fate conversion can lead to metaplasia and cancer.
- The ATM-p53 pathway is a critical regulator of cellular stress responses.
Purpose of the Study:
- To investigate the cellular response to extensive chromatin opening during cell reprogramming.
- To identify the molecular players involved in sensing and responding to chromatin remodeling.
- To elucidate the role of this response in preventing potentially oncogenic cell fate changes.
Main Methods:
- Utilized cell reprogramming models.
- Investigated the function of the Baf60b-containing chromatin remodeling complex.
- Analyzed the activation of the ATM-p53 pathway in response to chromatin changes.
Main Results:
- Transcription factor-induced chromatin opening during reprogramming is detected by the Baf60b complex.
- This detection activates the ATM-p53 pathway.
- The activated pathway leads to cell death, establishing a 'chromatin remodeling checkpoint'.
Conclusions:
- A novel checkpoint mechanism, the 'chromatin remodeling checkpoint', prevents inappropriate cell fate conversion.
- This checkpoint utilizes the Baf60b complex and ATM-p53 pathway to eliminate cells undergoing extensive chromatin opening.
- This process acts as a safeguard against metaplasia and cancer development initiated by tissue damage and subsequent aberrant reprogramming.