OCT4 and SOX2 work as transcriptional activators in reprogramming human fibroblasts Journal Article

Authors: Narayan, S.; Bryant, G.; Shah, S.; Berrozpe, G.; Ptashne, M.
Article Title: OCT4 and SOX2 work as transcriptional activators in reprogramming human fibroblasts
Abstract: SOX2 and OCT4, in conjunction with KLF4 and cMYC, are sufficient to reprogram human fibroblasts to induced pluripotent stem cells (iPSCs), but it is unclear if they function as transcriptional activators or as repressors. We now show that, like OCT4, SOX2 functions as a transcriptional activator. We substituted SOX2-VP16 (a strong activator) for wild-type (WT) SOX2, and we saw an increase in the efficiency and rate of reprogramming, whereas the SOX2-HP1 fusion (a strong repressor) eliminated reprogramming. We report that, at an early stage of reprogramming, virtually all DNA-bound OCT4, SOX2, and SOX2-VP16 were embedded in putative enhancers, about half of which were created de novo. Those associated with SOX2-VP16 were, on average, stronger than those bearing WT SOX2. Many newly created putative enhancers were transient, and many transcription factor locations on DNA changed as reprogramming progressed. These results are consistent with the idea that, during reprogramming, there is an intermediate state that is distinct from both parental cells and iPSCs. © 2017 The Authors
Keywords: transcription factors; transcription; stem cells; reprogramming; enhancers; ipscs
Journal Title: Cell Reports
Volume: 20
Issue: 7
ISSN: 2211-1247
Publisher: Cell Press  
Date Published: 2017-08-15
Start Page: 1585
End Page: 1596
Language: English
DOI: 10.1016/j.celrep.2017.07.071
PROVIDER: scopus
PUBMED: 28813671
PMCID: PMC5648000
Notes: Article -- Export Date: 5 September 2017 -- Source: Scopus
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MSK Authors
  1. Mark Ptashne
    61 Ptashne
  2. Gene Bryant
    14 Bryant
  3. Shivang S Shah
    4 Shah