Trichostatin A affects histone acetylation and gene expression in porcine somatic cell nucleus transfer embryos

Cervera, Rita P.; Martí-Gutiérrez, Nuria; Escorihuela, E.; Moreno, Ruben F.; Stojković, Miodrag

doi:10.1016/j.theriogenology.2009.06.030

Cited by 82 publications

(77 citation statements)

References 55 publications

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“…In bovine SCNT embryos treated with Oxamflatin, the Oct4 expression level was significantly higher than in the IVF group at the blastocyst stage [37]. Similar to the finding from the present study, porcine embryos treated with TSA appeared to have a similar Oct4 expression level compared with IVF embryos at the blastocyst stage [38]. The different Oct4 expression levels observed in embryos treated with a histone deacetylase inhibitor may be result of different treatment compounds and differing culture condition.…”

Section: Discussionsupporting

confidence: 85%

Scriptaid affects histone acetylation and the expression of development-related genes at different stages of porcine somatic cell nuclear transfer embryo during early development

et al. 2013

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Although the somatic cell nuclear transfer (SCNT) technique has been used extensively for cloning and generating transgenic pigs, the cloning efficiency is still very low. It has been proposed that the low efficiency of this technique is the result of incomplete epigenetic reprogramming and abnormal gene expression during early embryonic development. In this study, we investigate the effect of Scriptaid, a low-toxicity histone deacetylase inhibitor, on the developmental competence of porcine SCNT embryos. We found that treating SCNT embryos with 500 nmol/L Scriptaid for 15 h after activation significantly enhanced the blastocyst formation rate (27.7%) compared with the untreated group (control) (12.2%, P<0.05). Using an immunofluorescence technique to measure the average fluorescence intensity, we also found that treating SCNT embryos with Scriptaid increased the level of histone acetylation on histone H3 at lysine 14 (acH3K14). Furthermore, treating embryos with Scriptaid increased the expression level of three genes that play important roles during embryonic development (Oct4, Klf4 at the blastocyst stage and Nanog at the 4-cell stage). Moreover, the expression level of the apoptosis-related gene Caspase-3 was significantly lower in the Scriptaid-treated SCNT embryos compared with the control SCNT embryos at the 4-cell and blastocyst stages. In conclusion, these results indicate that Scriptaid treatment improves the development and nuclear reprogramming of porcine SCNT embryos.

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Section: Discussionsupporting

confidence: 85%

Scriptaid affects histone acetylation and the expression of development-related genes at different stages of porcine somatic cell nuclear transfer embryo during early development

et al. 2013

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“…On the other hand, recent studies for bovine SCNT showed that treating activated SCNT embryos with 50 nM TSA for 12 to 13 h had no significant effective on embryo development, although the blastocyst rates were somewhat improved [47,48]. This variability among laboratories and animals regarding the effects of TSA on SCNT embryo development could be related to species-specific effects of TSA, the concentration used, the moment of treatment, the duration of treatment or the somatic cell used as the nucleus donor [49]. The present study investigated the patterns of reshaping of glo- bal histone acetylation for reprogramming of somatic chromatin in the oocyte cytoplasm.…”

Section: Discussionmentioning

confidence: 99%

Trichostatin A Promotes the Development of Bovine Somatic Cell Nuclear Transfer Embryos

Lee

Kim

Lee

et al. 2011

Journal of Reproduction and Development

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Abstract. We studied the effects of trichostatin A (TSA), a histone deacetylase inhibitor, on the development of bovine somatic cell nuclear transfer (SCNT) embryos by investigating (1) the optimal concentration and treatment time of TSA for development of bovine SCNT embryos, (2) the status of histone acetylation in TSA-treated and control SCNT embryos and (3) the expression of histone acetylation-and deacetylation-related genes in TSA-treated and control SCNT embryos. We observed that 50 nM TSA-treatment for 20 h following fusion resulted in more efficient in vitro development of bovine SCNT embryos to the blastocyst stage. In regard to histone H4K5 acetylation, half of the control SCNT embryos faintly displayed histone H4K5 signals 30 min after electrofusion, while most of the TSA-treated SCNT embryos displayed histone H4K5 signals within 30 min after electrofusion. Furthermore, the expressions of HDAC1 and HDAC2 in the blastocysts were significantly lower (P<0.05) in the TSA-treated SCNT than in the control SCNT. However, the expression of GCN5 and HAT1 did not differ between the TSA-treated and control SCNT. In conclusion, we demonstrated that TSA-treatment after SCNT in bovine embryos can dramatically improve the practical applications of current cloning techniques. the survival rates to birth for cloned blastocysts is only 1 to 5% compared with a 30 to 60% birthrate for in vitro fertilization (IVF) blastocysts [11]. A serious impediment to the practical use of SCNT techniques is the low viability of cloned embryos during embryonic development; only a few percent of reconstructed oocytes develop to term, and of those, many die shortly after birth [5][6][7]12]. Even the surviving offspring show large placentas [7,[13][14][15] and increased birth weights [16], a phenomenon referred to as "large offspring syndrome" (LOS). Furthermore, some offspring with a seemingly healthy appearance suffer from immune dysfunction or kidney/brain malformations, which contribute to death [3,17].It is, however, unclear whether the development failures of cloned embryos are due to incomplete nuclear reprogramming or the cloning procedure itself. Nuclear transfer involves a series of complex procedures including culture of donor cells, in vitro maturation of oocytes, enucleation, cell or nuclear injection, fusion, activation, in vitro culture of reconstructed embryos and embryo transfer [18]. If any component of these steps is suboptimal, the production of cloned embryos or animals can be influenced. Reprogramming events following the transfer of somatic nuclei into oocyte cytoplasm occur at the epigenetic level. One of the many currently known epigenetic modalities is the global level and local pattern of acetylation of nuclear histones [19]. The extent to which reprogramming after nuclear transfer (NT) depends upon reshaping by histone acetylation, if at all, is not clear. Increased histone acetylation levels in most amino acid residues lead to loose binding of the nucleosome to DNA and/or linker histones, relaxation of the ch...

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“…In the present study, the level of FGF4 transcripts in SCNT embryos was unchanged by TSA treatment and was maintained at a lower level. Several investigators have reported that the transcript levels of some genes did not change in bovine or porcine SCNT embryos after treatment with TSA [23,28,41]. Although the reason for this difference in sensitivity to TSA treatment is not clear, it is possible that other epigenetic factors, such as DNA methylation, in each gene influence the transcript levels.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Status and Full-term Development of Bovine Cloned Embryos Treated with Trichostatin A

Sawai

Fujii

Hirayama

et al. 2012

Journal of Reproduction and Development

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Abstract. We examined the comprehensive epigenetic status, including histone H3 and H4 acetylation, DNA methylation and level of mRNA transcripts of bovine somatic cell nuclear transfer (SCNT) embryos treated with trichostatin A (TSA), along with their full-term developmental efficacy. Treatment with 50 nM TSA enhanced early developmental competence; increased acetylation of two histones, H3K9K14 and H4K8, at the blastocyst stage; and maintained the DNA methylation status of the satellite I sequence in bovine SCNT embryos. The difference in IGFBP-3 transcript levels between in vivo and SCNT embryos disappeared in SCNT embryos after treatment with 50 nM TSA. Pregnancy, full-term developmental competence and body weight at birth of offspring did not differ between SCNT embryos treated with 50 nM TSA and untreated embryos. These results suggest that treatment with TSA improves preimplantation development and changes the epigenetic status but does not promote the full-term development competence in bovine SCNT embryos. Key words: Bovine embryo, Gene expression, Histone modification, Nuclear transfer, TSA (J. Reprod. Dev. 58: [302][303][304][305][306][307][308][309] 2012) T he efficiency of animal production by somatic cell nuclear transfer (SCNT) is still very low. In bovine cloning, high rates of embryonic, fetal, neonatal and postnatal abnormalities have consistently been observed [1][2][3][4][5][6]. Although the cause of such abnormalities is unknown, the phenomenon may be correlated with abnormal gene expression [7], because several investigators have reported aberant transcription patterns of various genes that have an important role in pre-or postimplantation development in bovine SCNT embryos [8][9][10][11][12][13]. Moreover, an aberrant pattern of gene expression is persistently observed in bovine SCNT embryos that develop to the elongated stage and into a conceptus after implantation [11,12,14,15].The characteristics of gene transcription in SCNT embryos can be attributed to abnormalities in the control system for gene expression such as DNA methylation [16][17][18][19] and acetylation of histones [20]. Kang et al. [16,18] reported that various repeated genomic sequences, including satellite I, were barely demethylated in bovine SCNT embryos at the blastocyst stage. The methylation patterns observed in such embryos closely resembled those in donor cells but were quite different from those in normal embryos produced in vivo or in vitro. These findings suggest dysregulation of epigenetic modifications, such as DNA methylation, resulting in abnormal transcription of developmentally crucial genes at the blastocyst stage.Recently, it was clearly demonstrated in mice that histone modifications are closely related to the success rate of cloning [21,22]. It was reported that treatment with trichostatin A (TSA), which is a histone deacetylase inhibitor, improves in vitro blastocyst development, embryonic stem cell derivation and full-term development of mouse SCNT embryos. Furthermore, TSA treatment also improves...

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Trichostatin A affects histone acetylation and gene expression in porcine somatic cell nucleus transfer embryos

Cited by 82 publications

References 55 publications

Scriptaid affects histone acetylation and the expression of development-related genes at different stages of porcine somatic cell nuclear transfer embryo during early development

Scriptaid affects histone acetylation and the expression of development-related genes at different stages of porcine somatic cell nuclear transfer embryo during early development

Trichostatin A Promotes the Development of Bovine Somatic Cell Nuclear Transfer Embryos

Epigenetic Status and Full-term Development of Bovine Cloned Embryos Treated with Trichostatin A

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