Trichostatin A treatment of cloned mouse embryos improves constitutive heterochromatin remodeling as well as developmental potential to term.
BACKGROUND
Genome reprogramming in early mouse embryos is associated with nuclear reorganization and particular features such as the peculiar distribution of centromeric and pericentric heterochromatin during the first developmental stage. This zygote-specific heterochromatin organization could be observed both in maternal and paternal pronuclei after natural fertilization as well as in embryonic stem (ES) cell nuclei after nuclear transfer suggesting that this particular type of nuclear organization was essential for embryonic reprogramming and subsequent development.


RESULTS
Here, we show that remodeling into a zygotic-like organization also occurs after somatic cell nuclear transfer (SCNT), supporting the hypothesis that reorganization of constitutive heterochromatin occurs regardless of the source and differentiation state of the starting material. However, abnormal nuclear remodeling was frequently observed after SCNT, in association with low developmental efficiency. When transient treatment with the histone deacetylase inhibitor trichostatin A (TSA) was tested, we observed improved nuclear remodeling in 1-cell SCNT embryos that correlated with improved rates of embryonic development at subsequent stages.


CONCLUSIONS
Together, the results suggest that proper organization of constitutive heterochromatin in early embryos is involved in the initial developmental steps and might have long term consequences, especially in cloning procedures.
Maalouf
Walid E
WE
INRA, UMR 1198 Biologie du Développement et Reproduction, Jouy en Josas, France. walidemaalouf@yahoo.co.uk
Liu
Zichuan
Z
Brochard
Vincent
V
Renard
Jean-Paul
JP
Debey
Pascale
P
Beaujean
Nathalie
N
Zink
Daniele
D
D000818:Animals; D002453:Cell Cycle; D042002:Chromatin Assembly and Disassembly; D004622:Embryo, Mammalian / Q000378:metabolism; D047108:Embryonic Development / Q000187:drug effects*; D006570:Heterochromatin / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000494:pharmacology*; D051379:Mice; D053652:Nuclear Transfer Techniques
D006570:Heterochromatin; D006877:Hydroxamic Acids; C012589:trichostatin A