title: Trichostatin A modified histone covalent pattern and enhanced expression of pluripotent genes in interspecies black-footed cat cloned embryos but did not improve in vitro and in vivo viability.
abstract: Abstract The black-footed cat (BFC; Felis nigripes), one of the smallest wild cats, is listed as threatened. Interspecies somatic cell nuclear transfer (Is-SCNT) offers the possibility of preserving endangered species. Development to term of interspecies BFC (Is-BFC) cloned embryos has not been obtained, possibly due to abnormal epigenetic reprogramming. Treatment of intraspecies cloned embryos with TSA improves nuclear reprogramming and in vitro and in vivo viability. In this study, we evaluated (1) whether covalent histone modifications differ between Is-BFC cloned embryos and their IVF counterparts, (2) the optimal TSA concentration and exposure times to modify the covalent histone patterns, (3) if TSA enhances in vitro and in vivo developmental competence of cloned embryos, and (4) expression of pluripotent genes. Results indicated that the covalent histone modifications of Is-BFC cloned embryos aberrantly differ from their DSH-IVF counterpart embryos. Aberrant epigenetic events may be due partially to the inability of the DSH cytoplasm to modify the restrictive epigenetic marks of the BFC nuclei after somatic cell nuclear transfer (SCNT). Incomplete remodeling of the histone H3K9me2 in Is-BFC cloned embryos possibly contributes to abnormal expression of pluripotent genes and low embryonic development. Treatment of Is-BFC cloned embryos with TSA remodeled the covalent pattern in H3K9ac and H3K9me2, resembling epigenetic patterns in IVF counterpart embryos, and resulted in activation of some pluripotent genes. However, genomic reprogramming of Is-BFC cloned blastocysts did not follow the same reprogramming pattern observed in DSH-IVF embryos, and in vitro and in vivo developmental competence was not enhanced.
authors: Audubon Center for Research of Endangered Species, New Orleans, Louisiana, USA. mgomez@auduboninstitute.org
authors: Martha C
authors: MC
authors: Gómez
authors: C Earle
authors: CE
authors: Pope
authors: Monica N
authors: MN
authors: Biancardi
authors: Cherie
authors: C
authors: Dumas
authors: Jason
authors: J
authors: Galiguis
authors: Anna Claire
authors: AC
authors: Morris
authors: Guoshun
authors: G
authors: Wang
authors: Betsy L
authors: BL
authors: Dresser
mesh_terms: D000818:Animals; D002415:Cats / Q000196:embryology* / Q000235:genetics*; D065150:Cellular Reprogramming; D019976:Cloning, Organism; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D005307:Fertilization in Vitro; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006657:Histones / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008297:Male; D053652:Nuclear Transfer Techniques / Q000662:veterinary; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000502:physiology*
chemical_list: D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; C012589:trichostatin A