Template Activating Factor-I α Regulates Retroviral Silencing during Reprogramming

Phuong Linh Bui, Ken Nishimura, Gonzalo Seminario Mondejar, Arun Kumar, Shiho Aizawa, Kensaku Murano, Kyosuke Nagata, Yohei Hayashi, Aya Fukuda, Yasuko Onuma, Yuzuru Ito, Mahito Nakanishi, Koji Hisatake

Research output: Contribution to journalArticle

Abstract

Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) is accompanied by dramatic changes in epigenetic programs, including silencing of endogenous and exogenous retroviruses. Here, we utilized replication-defective and persistent Sendai virus (SeVdp)-based vectors to monitor retroviral silencing during reprogramming. We observed that retroviral silencing occurred at an early reprogramming stage without a requirement for KLF4 or the YY1-binding site in the retroviral genome. Insertional chromatin immunoprecipitation (iChIP) enabled us to isolate factors assembled on the silenced provirus, including components of inhibitor of histone acetyltransferase (INHAT), which includes the SET/TAF-I oncoprotein. Knockdown of SET/TAF-I in mouse embryonic fibroblasts (MEFs) diminished retroviral silencing during reprogramming, and overexpression of template activating factor-I α (TAF-Iα), a SET/TAF-I isoform predominant in embryonic stem cells (ESCs), reinforced retroviral silencing by an SeVdp-based vector that is otherwise defective in retroviral silencing. Our results indicate an important role for TAF-Iα in retroviral silencing during reprogramming.

Original languageEnglish
Pages (from-to)1909-1922.e5
JournalCell Reports
Volume29
Issue number7
DOIs
Publication statusPublished - 2019 Nov 12

Keywords

  • SeVdp vector
  • TAF-Iα
  • insertional chromatin immunoprecipitation
  • primer-binding site
  • reprogramming
  • retroviral silencing

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Bui, P. L., Nishimura, K., Seminario Mondejar, G., Kumar, A., Aizawa, S., Murano, K., Nagata, K., Hayashi, Y., Fukuda, A., Onuma, Y., Ito, Y., Nakanishi, M., & Hisatake, K. (2019). Template Activating Factor-I α Regulates Retroviral Silencing during Reprogramming. Cell Reports, 29(7), 1909-1922.e5. https://doi.org/10.1016/j.celrep.2019.10.010