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Template Activating Factor-I α Regulates Retroviral Silencing during Reprogramming
Phuong Linh Bui1, Ken Nishimura1, Gonzalo Seminario Mondejar1
1Laboratory of Gene Regulation, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
Cell Reports
|November 14, 2019
Summary
Induced pluripotent stem cells (iPSCs) reprogramming silences retroviruses early. SET/TAF-I, particularly TAF-Iα, is crucial for this retroviral silencing during cell reprogramming.
Area of Science:
- Epigenetics
- Stem Cell Biology
- Virology
Background:
- Cellular reprogramming to induced pluripotent stem cells (iPSCs) involves significant epigenetic alterations.
- Silencing of retroviruses, both endogenous and exogenous, is a key epigenetic event during reprogramming.
Purpose of the Study:
- To investigate the mechanisms of retroviral silencing during somatic cell reprogramming.
- To identify key factors involved in retroviral silencing using Sendai virus-based vectors.
Main Methods:
- Utilized replication-defective and persistent Sendai virus (SeVdp)-based vectors to monitor retroviral silencing.
- Employed insertional chromatin immunoprecipitation (iChIP) to identify proteins bound to silenced proviruses.
- Performed knockdown of SET/TAF-I and overexpression of TAF-Iα in mouse embryonic fibroblasts (MEFs).
Main Results:
- Retroviral silencing was observed at an early stage of reprogramming, independent of KLF4 or YY1-binding sites.
- Components of inhibitor of histone acetyltransferase (INHAT), including SET/TAF-I, were identified on silenced proviruses.
- SET/TAF-I knockdown impaired retroviral silencing, while TAF-Iα overexpression enhanced it.
Conclusions:
- TAF-Iα plays a critical role in mediating retroviral silencing during the reprogramming of somatic cells to iPSCs.
- The findings highlight the importance of INHAT components in epigenetic regulation during cell reprogramming.
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