title: Latrunculin A treatment prevents abnormal chromosome segregation for successful development of cloned embryos.
abstract: Somatic cell nuclear transfer to an enucleated oocyte is used for reprogramming somatic cells with the aim of achieving totipotency, but most cloned embryos die in the uterus after transfer. While modifying epigenetic states of cloned embryos can improve their development, the production rate of cloned embryos can also be enhanced by changing other factors. It has already been shown that abnormal chromosome segregation (ACS) is a major cause of the developmental failure of cloned embryos and that Latrunculin A (LatA), an actin polymerization inhibitor, improves F-actin formation and birth rate of cloned embryos. Since F-actin is important for chromosome congression in embryos, here we examined the relation between ACS and F-actin in cloned embryos. Using LatA treatment, the occurrence of ACS decreased significantly whereas cloned embryo-specific epigenetic abnormalities such as dimethylation of histone H3 at lysine 9 (H3K9me2) could not be corrected. In contrast, when H3K9me2 was normalized using the G9a histone methyltransferase inhibitor BIX-01294, the Magea2 gene-essential for normal development but never before expressed in cloned embryos-was expressed. However, this did not increase the cloning success rate. Thus, non-epigenetic factors also play an important role in determining the efficiency of mouse cloning.
authors.affiliation: Laboratory for Genomic Reprogramming, Center for Developmental Biology, RIKEN, Kobe, Japan ; Laboratory of Animal Reproduction, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Terashita
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamagata
authors.forename: Mikiko
authors.initials: M
authors.lastname: Tokoro
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Itoi
authors.forename: Sayaka
authors.initials: S
authors.lastname: Wakayama
authors.forename: Chong
authors.initials: C
authors.lastname: Li
authors.forename: Eimei
authors.initials: E
authors.lastname: Sato
authors.forename: Kentaro
authors.initials: K
authors.lastname: Tanemura
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Wakayama
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D020090:Chromosome Segregation / Q000187:drug effects* / Q000235:genetics*; D019976:Cloning, Organism / Q000379:methods; D004622:Embryo, Mammalian / Q000187:drug effects* / Q000378:metabolism; D047108:Embryonic Development / Q000187:drug effects* / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000187:drug effects / Q000235:genetics; D005260:Female; D005307:Fertilization in Vitro; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008745:Methylation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D053652:Nuclear Transfer Techniques; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology; D053778:Thiazolidines / Q000494:pharmacology*
chemical_list: D000199:Actins; D001381:Azepines; C518299:BIX 01294; D019086:Bridged Bicyclo Compounds, Heterocyclic; D006657:Histones; D011799:Quinazolines; D053778:Thiazolidines; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine; C037067:latrunculin A