title: Trichostatin A specifically improves the aberrant expression of transcription factor genes in embryos produced by somatic cell nuclear transfer.
abstract: Although mammalian cloning by somatic cell nuclear transfer (SCNT) has been established in various species, the low developmental efficiency has hampered its practical applications. Treatment of SCNT-derived embryos with histone deacetylase (HDAC) inhibitors can improve their development, but the underlying mechanism is still unclear. To address this question, we analysed gene expression profiles of SCNT-derived 2-cell mouse embryos treated with trichostatin A (TSA), a potent HDAC inhibitor that is best used for mouse cloning. Unexpectedly, TSA had no effect on the numbers of aberrantly expressed genes or the overall gene expression pattern in the embryos. However, in-depth investigation by gene ontology and functional analyses revealed that TSA treatment specifically improved the expression of a small subset of genes encoding transcription factors and their regulatory factors, suggesting their positive involvement in de novo RNA synthesis. Indeed, introduction of one of such transcription factors, Spi-C, into the embryos at least partially mimicked the TSA-induced improvement in embryonic development by activating gene networks associated with transcriptional regulation. Thus, the effects of TSA treatment on embryonic gene expression did not seem to be stochastic, but more specific than expected, targeting genes that direct development and trigger zygotic genome activation at the 2-cell stage.
authors.affiliation: 1] Bioresource Center, RIKEN, 3-1-1 Koyadai, Tsukuba, Ibaraki, 305-0074 Japan [2] Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Ten-noudai, Tsukuba, Ibaraki, 305-8572 Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Bioresource Center, RIKEN, 3-1-1 Koyadai, Tsukuba, Ibaraki, 305-0074 Japan.
authors.forename: Mami
authors.initials: M
authors.lastname: Oikawa
authors.affiliation: 1] Bioresource Center, RIKEN, 3-1-1 Koyadai, Tsukuba, Ibaraki, 305-0074 Japan [2] Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Ten-noudai, Tsukuba, Ibaraki, 305-8572 Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kamimura
authors.affiliation: Bioresource Center, RIKEN, 3-1-1 Koyadai, Tsukuba, Ibaraki, 305-0074 Japan.
authors.forename: Narumi
authors.initials: N
authors.lastname: Ogonuki
authors.affiliation: Department of Pathology, Medical School and Graduate School of Frontier Biosciences, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871 Japan.
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Pathology, Medical School and Graduate School of Frontier Biosciences, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871 Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Nakano
authors.affiliation: 1] Bioresource Center, RIKEN, 3-1-1 Koyadai, Tsukuba, Ibaraki, 305-0074 Japan [2] Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Ten-noudai, Tsukuba, Ibaraki, 305-8572 Japan.
authors.forename: Kuniya
authors.initials: K
authors.lastname: Abe
authors.affiliation: 1] Bioresource Center, RIKEN, 3-1-1 Koyadai, Tsukuba, Ibaraki, 305-0074 Japan [2] Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Ten-noudai, Tsukuba, Ibaraki, 305-8572 Japan.
authors.forename: Atsuo
authors.initials: A
authors.lastname: Ogura
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004624:Embryo Transfer / Q000379:methods; D004622:Embryo, Mammalian / Q000196:embryology; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006877:Hydroxamic Acids / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D053652:Nuclear Transfer Techniques; D020411:Oligonucleotide Array Sequence Analysis; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C423918:Spic protein, mouse; D014157:Transcription Factors; C012589:trichostatin A