Template Activating Factor-I α Regulates Retroviral Silencing during Reprogramming

Cell Rep. 2019 Nov 12;29(7):1909-1922.e5. doi: 10.1016/j.celrep.2019.10.010.


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.

Keywords: SeVdp vector; TAF-Iα; insertional chromatin immunoprecipitation; primer-binding site; reprogramming; retroviral silencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cellular Reprogramming Techniques*
  • Cellular Reprogramming*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Endogenous Retroviruses* / genetics
  • Endogenous Retroviruses* / metabolism
  • Gene Silencing*
  • Histone Chaperones / genetics
  • Histone Chaperones / metabolism
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • Mice
  • Mouse Embryonic Stem Cells* / cytology
  • Mouse Embryonic Stem Cells* / metabolism
  • Mouse Embryonic Stem Cells* / virology
  • Sendai virus / genetics
  • Sendai virus / metabolism
  • YY1 Transcription Factor / genetics
  • YY1 Transcription Factor / metabolism


  • DNA-Binding Proteins
  • Histone Chaperones
  • Klf4 protein, mouse
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors
  • SET protein, mouse
  • YY1 Transcription Factor
  • Yy1 protein, mouse