RRC ID 34801
Author Inoue K, Oikawa M, Kamimura S, Ogonuki N, Nakamura T, Nakano T, Abe K, Ogura A.
Title Trichostatin A specifically improves the aberrant expression of transcription factor genes in embryos produced by somatic cell nuclear transfer.
Journal Sci Rep
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.
Volume 5
Pages 10127
Published 2015-5-14
DOI 10.1038/srep10127
PII srep10127
PMID 25974394
PMC PMC4431350
MeSH Animals DNA-Binding Proteins / biosynthesis DNA-Binding Proteins / genetics Embryo Transfer / methods Embryo, Mammalian / embryology Embryonic Development / drug effects* Female Gene Expression / drug effects Gene Expression Profiling Gene Expression Regulation, Developmental / drug effects Histone Deacetylase Inhibitors / pharmacology* Hydroxamic Acids / pharmacology* Mice Mice, Inbred C57BL Mice, Inbred DBA Mice, Inbred ICR Molecular Sequence Data Nuclear Transfer Techniques* Oligonucleotide Array Sequence Analysis Transcription Factors / biosynthesis* Transcription Factors / genetics Transcription, Genetic / genetics
IF 3.998
Times Cited 18
DNA material pcDNA4 Myc-HisA-Spic (RDB13502) pcDNA4 Myc-HisA-Spic-GFP (RDB13503).