Valproic Acid Improves Porcine Parthenogenetic Embryo Development Through Transient Remodeling of Histone Modifiers

Huang, Yongye; Yuan, Lin; Li, Tianye; Wang, Anfeng; Li, Zhanjun; Pang, Daxin; Wang, Bing; Ouyang, Hongsheng

doi:10.1159/000438515

Cited by 8 publications

(5 citation statements)

References 20 publications

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“…We observed absence or weak fluorescent intensity for H3K27me2 in zygotes, which differs from previous studies in mice reporting intensive H3K27me2 signal in PNs of mice zygotes (Erhardt et al, 2003). Conversely, we observed a prominent fluorescent signal for H3K27me2 in D6 and D8 IVF blastocysts, while another study reported that H3K27me2 levels were nearly undetectable in porcine blastocysts produced by parthenogenetic activation (Huang et al, 2015). Differences between fertilized and parthenogenetic embryos have been reported regarding other histone modifications including H3K9ac and H3K27ac (Huang et al, 2015).…”

Section: Discussioncontrasting

confidence: 99%

Acetylation and methylation profiles of H3K27 in porcine embryos cultured in vitro

Marinho

Rissi

Lindquist

et al. 2017

Zygote

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Methylation and acetylation of histone H3 at lysine 27 (H3K27) regulate chromatin structure and gene expression during early embryo development. While H3K27 acetylation (H3K27ac) is associated with active gene expression, H3K27 methylation (H3K27me) is linked to transcriptional repression. The aim of this study was to assess the profile of H3K27 acetylation and methylation (mono-, di- and trimethyl) during oocyte maturation and early development in vitro of porcine embryos. Oocytes/embryos were fixed at different developmental stages from germinal vesicle to day 8 blastocysts and submitted to an immunocytochemistry protocol to identify the presence and quantify the immunofluorescence intensity of H3K27ac, H3K27me1, H3K27me2 and H3K27me3. A strong fluorescent signal for H3K27ac was observed in all developmental stages. H3K27me1 and H3K27me2 were detected in oocytes, but the fluorescent signal decreased through the cleavage stages and rose again at the blastocyst stage. H3K27me3 was detected in oocytes, in only one pronucleus in zygotes, cleaved-stage embryos and blastocysts. The nuclear fluorescence signal for H3K27me3 increased from the 2-cell stage to 4-cell stage embryos, decreased at the 8-cell and morula stages and increased again in blastocysts. Different patterns of the H3K27me3 mark were observed at the blastocyst stage. Our results suggest that changes in the H3K27 methylation status regulate early porcine embryo development as previously shown in other species.

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Section: Discussioncontrasting

confidence: 99%

Acetylation and methylation profiles of H3K27 in porcine embryos cultured in vitro

Marinho

Rissi

Lindquist

et al. 2017

Zygote

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“…HDAC inhibitors are being increasingly used in IVC treatment for improving the efficiency of SCNT and parthenogenetic activation [42]. In this study, we sought to improve the development of porcine SCNT embryos with LAQ824 (class I, IIa and IIb HDAC inhibitor) treatment.…”

Section: Discussionmentioning

confidence: 99%

The HDAC Inhibitor LAQ824 Enhances Epigenetic Reprogramming and In Vitro Development of Porcine SCNT Embryos

Jin

Lee

Taweechaipaisankul

et al. 2017

Cell Physiol Biochem

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Background/Aims: Hypoacetylation caused by aberrant epigenetic nuclear reprogramming results in low efficiency of mammalian somatic cell nuclear transfer (SCNT). Many epigenetic remodeling drugs have been used in attempts to improve in vitro development of porcine SCNT embryos. In this study, we examined the effects of LAQ824, a structurally novel histone acetylase inhibitor, on the nuclear reprogramming and in vitro development of porcine SCNT embryos. Methods: LAQ824 treatment was supplemented during the culture of SCNT embryos. The reprogramming levels were measured by immunofluorescence and quantified by image J software. Relative expression levels of 18 genes were analyzed by quantitative real-time PCR. Results: 100 nM LAQ824 treatment of post-activation SCNT embryos for 24 h significantly improved the subsequent blastocyst formation rate. The LAQ824 treatment enhanced histone 3 lysine 9 (H3K9) levels, histone 4 lysine 12 (H4K12) levels, and reduced global DNA methylation levels as well as anti-5-methylcytosine (5-mC) at the pseudo-pronuclear and 2-cell stages. Furthermore, LAQ824 treatment positively regulated the mRNA expression of genes for histone acetylation (HAT1, HDAC1, 2, 3, and 6), DNA methylation (DNMT1, 3a and 3b), development (Pou5f1, Nanog, Sox2, and GLUT1) and apoptosis (Bax, Bcl2, Caspase 3 and Bak) in blastocysts. Conclusion: Optimum exposure (100 nM for 24 h) to LAQ824 post-activation improved the in vitro development of porcine SCNT embryos by enhancing levels of H3K9 and H4K12, reducing 5-mC, and regulating gene expression.

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“…We found that VPA induces increased levels of H3K4me2/me3 and H3K9me markers, which are associated with active gene transcription and have been previously reported after treatment with HDAC inhibitors, including VPA, in HL60 cells, mouse embryonic stem cells, primary blast cells of patients with acute myeloid leukemia, rat astrocytes and cortical neurons, fibroblasts, human breast cancer cells, pig embryos, rat hippocampus and a human leukemia cell line [20,[48][49][50][67][68][69][70][71]. The abundance of H3K4me2/me3 in the presence of VPA in HeLa cells was associated with increased gene expression of the methyltransferase KMT2D.…”

Section: Discussionsupporting

confidence: 75%

Efeitos do Valproato de Sódio nos níveis de metilações da histona H3, na interação VPA-histonas e na regulação dos genes p16ink4a e p21waf1/cip1 em células HeLa

Amorim Rocha

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Agradeço à minha família que mesmo de longe emanava todo imenso amor.Gratidão por compreender e apoiar os meus sonhos! Meu sincero agradecimento à minha mãe Maricelia Risério Amorim pela confiança, suporte, carinho, e por todo o incentivo que sempre me foi dado. Ao meu pai Marcelino Rocha de Jesus por ser meu exemplo de caráter, disciplina e perseverança. Às minhas queridas irmãs e melhores amigas, Mariane Amorim Rocha e Mayara Amorim Santos pelos conselhos, ensinamentos e por me apoiarem, à minha sobrinha Maya Caires Amorim por toda alegria, aos meus saudosos avós, tios e primos.Ao meu grande amor e companheiro diário Bruno Luís Gonçalves da Cunha, pela força, otimismo, apoio e principalmente pela sua paciência e amor. Gratidão por tudo, por me ajudar a superar tantos momentos.Minha gratidão especial à Profa. Dra. Maria Luiza Silveira Mello, por me receber em seu grupo de pesquisa bem como por acreditar e confiar no meu trabalho. Agradeço por todas as oportunidades durante essa trajetória, além da sua tamanha contribuição científica e empenho ao longo de todos esses anos de trabalho que se iniciaram ainda no mestrado. Ao Prof. Dr. Benedicto de Campos Vidal, pelas conversas e importantes conhecimentos compartilhados, pelo exemplo de competência, disciplina e dedicação profissional.Sou grata também por aqueles com quem troquei vivências de laboratório. À amiga e bióloga Camila Borges M. de Oliveira que além de ter colaborado em procedimentos de rotina de cultura celular, compartilhou momentos de ansiedade, preocupações, aflições e felicidades aos dias de muito trabalho. Ao Dr. Douglas S. dos Santos por incentivar, compartilhar suas inúmeras experiências e pelos momentos descontraídos. Ao Eli Heber dos Anjos pelos ensinamentos em química. Sou muito grata ao amigo Dr. Nilton José dos Santos pela amizade e principalmente pela disponibilidade em ajudar nos momentos que mais precisei. Ao Dr.Adauto Lima Cardoso por aceitar participar, orientar e colaborar com parte dos desafios que envolveram esta pesquisa. À tantos amigos em especial à minha grande amiga Milene Marques pelos incentivos, longas conversas e palavras de conforto.

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Valproic Acid Improves Porcine Parthenogenetic Embryo Development Through Transient Remodeling of Histone Modifiers

Cited by 8 publications

References 20 publications

Acetylation and methylation profiles of H3K27 in porcine embryos cultured in vitro

Acetylation and methylation profiles of H3K27 in porcine embryos cultured in vitro

The HDAC Inhibitor LAQ824 Enhances Epigenetic Reprogramming and In Vitro Development of Porcine SCNT Embryos

Efeitos do Valproato de Sódio nos níveis de metilações da histona H3, na interação VPA-histonas e na regulação dos genes p16ink4a e p21waf1/cip1 em células HeLa

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