Document Detail

Histone deacetylase inhibitors improve in vitro and in vivo developmental competence of somatic cell nuclear transfer porcine embryos.
MedLine Citation:
PMID:  20132015     Owner:  NLM     Status:  MEDLINE    
Faulty epigenetic reprogramming of somatic nuclei is likely to be a major cause of low success observed in all mammals produced through somatic cell nuclear transfer (SCNT). It has been demonstrated that the developmental competence of SCNT embryos in several species were significantly enhanced via treatment of histone deacetylase inhibitors (HDACi) such as trichostatin A (TSA) to increase histone acetylation. Here we report that 50 nM TSA for 10 h after activation increased the developmental competence of porcine SCNT embryos constructed from Landrace fetal fibroblast cells (FFCs) in vitro and in vivo, but not at higher concentrations. Therefore, we optimized the application of another novel HDACi, Scriptaid, for development of porcine SCNT embryos. We found that treatment with 500 nM Scriptaid significantly enhanced the development SCNT embryos to the blastocyst stage when outbred Landrace FFCs and ear fibroblast cells (EFCs) were used as donors compared to the untreated group. Scriptaid increased the overall cloning efficiency from 0.4% (untreated group) to 1.6% for Landrace FFCs and 0 to 3.7% for Landrace EFCs. Moreover, treatment of SCNT embryos with Scriptaid improved the histone acetylation on Histone H4 at lysine 8 (AcH4K8) in a pattern similar to that of the in vitro fertilized (IVF) embryos.
Jianguo Zhao; Yanhong Hao; Jason W Ross; Lee D Spate; Eric M Walters; Melissa S Samuel; August Rieke; Clifton N Murphy; Randall S Prather
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Cellular reprogramming     Volume:  12     ISSN:  2152-4998     ISO Abbreviation:  Cell Reprogram     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-02-05     Completed Date:  2010-05-10     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  101528176     Medline TA:  Cell Reprogram     Country:  United States    
Other Details:
Languages:  eng     Pagination:  75-83     Citation Subset:  IM    
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MeSH Terms
Acetylation / drug effects
Animals, Outbred Strains
Blastocyst / cytology,  drug effects,  metabolism
Cloning, Organism
Dose-Response Relationship, Drug
Embryo Culture Techniques
Embryo Transfer / methods
Embryo, Mammalian / drug effects,  metabolism
Embryonic Development / drug effects*,  physiology
Enzyme Activation / drug effects
Histone Deacetylase Inhibitors / pharmacology*
Histone Deacetylases / metabolism
Hydroxamic Acids / pharmacology
Hydroxylamines / pharmacology
Nuclear Transfer Techniques / veterinary*
Quinolines / pharmacology
Sus scrofa / metabolism*
Time Factors
Grant Support
R01 RR013438/RR/NCRR NIH HHS; R01 RR013438-11/RR/NCRR NIH HHS; RR013438/RR/NCRR NIH HHS; RR018877/RR/NCRR NIH HHS; U42 RR018877-05/RR/NCRR NIH HHS
Reg. No./Substance:
0/Histone Deacetylase Inhibitors; 0/Hydroxamic Acids; 0/Hydroxylamines; 0/Quinolines; 0/scriptaid; 3X2S926L3Z/trichostatin A; EC Deacetylases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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