Document Detail

Role of histone acetylation in reprogramming of somatic nuclei following nuclear transfer.
MedLine Citation:
PMID:  16481594     Owner:  NLM     Status:  MEDLINE    
Before fertilization, chromatins of both mouse oocytes and spermatozoa contain very few acetylated histones. Soon after fertilization, chromatins of both gametes become highly acetylated. The same deacetylation-reacetylation changes occur with histones of somatic nuclei transferred into enucleated oocytes. The significance of these events in somatic chromatin reprogramming to the totipotent state is not known. To investigate their importance in reprogramming, we injected cumulus cell nuclei into enucleated mouse oocytes and estimated the histone deacetylation dynamics with immunocytochemistry. Other reconstructed oocytes were cultured before and/or after activation in the presence of the highly potent histone deacetylase inhibitor trychostatin A (TSA) for up to 9 h postactivation. The potential of TSA-treated and untreated oocytes to develop to the blastocyst stage and to full term was compared. Global deacetylation of histones in the cumulus nuclei occurred between 1 and 3 h after injection. TSA inhibition of histone deacetylation did not affect the blastocyst rate (37% with and 34% without TSA treatment), whereas extension of the TSA treatment beyond the activation point significantly increased the blastocyst rate (up to 81% versus 40% without TSA treatment) and quality (on average, 59 versus 45 cells in day 4 blastocysts with and without TSA treatment, respectively). TSA treatment also slightly increased full-term development (from 0.8% to 2.8%). Thus, deacetylation of somatic histones is not important for reprogramming, and hyperacetylation might actually improve reprogramming.
Andrei Rybouchkin; Yoko Kato; Yukio Tsunoda
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-02-15
Journal Detail:
Title:  Biology of reproduction     Volume:  74     ISSN:  0006-3363     ISO Abbreviation:  Biol. Reprod.     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-05-22     Completed Date:  2006-09-13     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0207224     Medline TA:  Biol Reprod     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1083-9     Citation Subset:  IM    
Laboratory of Animal Reproduction, College of Agriculture, Kinki University, Nara 631-8505, Japan.
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MeSH Terms
Acetylation / drug effects
Blastocyst / cytology,  drug effects,  physiology
Cell Differentiation / drug effects,  physiology
Cell Nucleus / chemistry,  physiology*
Cells, Cultured
Embryonic Development / drug effects,  physiology*
Histone Deacetylase Inhibitors
Histone Deacetylases / physiology
Histones / analysis,  metabolism*
Hydroxamic Acids / pharmacology
Mice, Inbred Strains
Nuclear Transfer Techniques*
Oocytes / chemistry,  cytology,  drug effects,  physiology*
Reg. No./Substance:
0/Histone Deacetylase Inhibitors; 0/Histones; 0/Hydroxamic Acids; 58880-19-6/trichostatin A; EC Deacetylases

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