PMID- 30319048
OWN - NLM
STAT- MEDLINE
DCOM- 20190918
LR  - 20240410
IS  - 1557-8534 (Electronic)
IS  - 1547-3287 (Print)
IS  - 1547-3287 (Linking)
VI  - 27
IP  - 24
DP  - 2018 Dec 15
TI  - FACT Inhibition Blocks Induction But Not Maintenance of Pluripotency.
PG  - 1693-1701
LID - 10.1089/scd.2018.0150 [doi]
AB  - The histone chaperone facilitates chromatin transactions (FACT) is associated 
      with nuclear processes, including DNA transcription, replication, and repair. We 
      previously showed that FACT is transiently recruited to pluripotency-associated 
      target genes by newly bound Oct4. In this study, we tested the effects of FACT 
      depletion by knockout or chemical inhibition on the induction and maintenance of 
      pluripotency. Clustered regularly interspaced short palindromic repeat 
      (CRISPR)-mediated deletion of the FACT subunit Spt16 did not affect the viability 
      or proliferation of fibroblasts but blocked their ability to form induced 
      pluripotent stem cells. Similarly, a small molecule inhibitor of FACT blocked the 
      induction of pluripotency at an early step in reprogramming, without affecting 
      the viability, proliferation, undifferentiated state, or the expression of core 
      pluripotency genes. Notably, trypsinization and passage of pluripotent cells 
      transiently reintroduced a requirement for FACT. Although FACT has been 
      considered to be an essential transcription elongation factor, these results 
      contribute to the emerging view that it instead promotes transitions between 
      stable chromatin states, including during reprogramming to pluripotency.
FAU - Shen, Zuolian
AU  - Shen Z
AD  - 1 Department of Pathology, University of Utah School of Medicine , Salt Lake 
      City, Utah.
FAU - Formosa, Tim
AU  - Formosa T
AD  - 2 Department of Biochemistry, University of Utah School of Medicine , Salt Lake 
      City, Utah.
FAU - Tantin, Dean
AU  - Tantin D
AD  - 1 Department of Pathology, University of Utah School of Medicine , Salt Lake 
      City, Utah.
LA  - eng
GR  - R01 GM064649/GM/NIGMS NIH HHS/United States
GR  - R01 GM122778/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20181128
PL  - United States
TA  - Stem Cells Dev
JT  - Stem cells and development
JID - 101197107
RN  - 0 (Chromatin)
RN  - 0 (Supt16 protein, mouse)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Cells, Cultured
MH  - *Cellular Reprogramming
MH  - Chromatin/metabolism
MH  - Mice
MH  - Pluripotent Stem Cells/*cytology
MH  - Transcription Factors/antagonists & inhibitors/genetics/*metabolism
PMC - PMC6302925
OTO - NOTNLM
OT  - FACT
OT  - embryonic stem cells
OT  - induced pluripotent stem cells
OT  - pluripotency
COIS- No competing financial interests exist.
EDAT- 2018/10/16 06:00
MHDA- 2019/09/19 06:00
PMCR- 2019/12/15
CRDT- 2018/10/16 06:00
PHST- 2018/10/16 06:00 [pubmed]
PHST- 2019/09/19 06:00 [medline]
PHST- 2018/10/16 06:00 [entrez]
PHST- 2019/12/15 00:00 [pmc-release]
AID - 10.1089/scd.2018.0150 [pii]
AID - 10.1089/scd.2018.0150 [doi]
PST - ppublish
SO  - Stem Cells Dev. 2018 Dec 15;27(24):1693-1701. doi: 10.1089/scd.2018.0150. Epub 
      2018 Nov 28.