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

R. P. Cervera; N. Martí-Gutiérrez; E. Escorihuela; R. Moreno; M. Stojkovic

doi:10.1016/j.theriogenology.2009.06.030

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

R. P. Cervera, N. Martí-Gutiérrez, E. Escorihuela, R. Moreno, M. Stojkovic

Research output: Contribution to journal › Article › peer-review

73 Scopus citations

Abstract

Epigenetic aberrancies likely preclude correct and complete nuclear reprogramming after somatic cell nucleus transfer (SCNT) and may underlie the observed reduced viability of cloned embryos. In the current study, we tested the effects of the histone deacetylase-inhibitor trichostatin A (TSA) on preimplantation development and on histone acetylation and the gene expression of nucleus transfer (NT) porcine (Sus scrofa) embryos. Our results showed that 5 nM TSA for 26 h after reconstitution resulted in embryos (NTTSA) that reached the blastocyst stage at a higher level (48.1% vs. 20.2%) and increased number of cells (105.0 vs. 75.3) than that of the control (NTC) embryos. In addition, and unlike the NTC embryos, the treated embryos displayed a global acetylated histone H4 at lysine 8 profile similar to the in vitro-fertilized (IVF) and cultured embryos during the preimplantation development. Finally, we determined that several transcription factors exert a dramatic amount of genetic control over pluripotency, including Oct4, Nanog, Cdx2, and Rex01, the imprinting genes Igf2 and Igf2r, and the histone deacetyltransferase gene Hdac2. The NT blastocysts showed similar levels of Oct4, Cdx2, and Hdac2 but lower levels of Nanog than those of the IVF blastocyst. However, the NTTSA blastocysts showed similar levels of Rex01, Igf2, and Igf2r as those of IVF blastocysts, whereas the NTC blastocysts showed significantly lower levels for those genes. Our results suggest that TSA improves porcine SCNT preimplantation development and affects the acetylated status of the H4K8, rendering acetylation levels similar to those of the IVF counterparts.

Original language	English (US)
Pages (from-to)	1097-1110
Number of pages	14
Journal	Theriogenology
Volume	72
Issue number	8
DOIs	https://doi.org/10.1016/j.theriogenology.2009.06.030
State	Published - Nov 2009
Externally published	Yes

Keywords

Acetylation
Histones
Nucleus transfer
Reprogramming
Trichostatin A

ASJC Scopus subject areas

Small Animals
Food Animals
Animal Science and Zoology
Equine

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10.1016/j.theriogenology.2009.06.030

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@article{f495983767fb4602b6fd9a4ba0bac977,

title = "Trichostatin A affects histone acetylation and gene expression in porcine somatic cell nucleus transfer embryos",

abstract = "Epigenetic aberrancies likely preclude correct and complete nuclear reprogramming after somatic cell nucleus transfer (SCNT) and may underlie the observed reduced viability of cloned embryos. In the current study, we tested the effects of the histone deacetylase-inhibitor trichostatin A (TSA) on preimplantation development and on histone acetylation and the gene expression of nucleus transfer (NT) porcine (Sus scrofa) embryos. Our results showed that 5 nM TSA for 26 h after reconstitution resulted in embryos (NTTSA) that reached the blastocyst stage at a higher level (48.1% vs. 20.2%) and increased number of cells (105.0 vs. 75.3) than that of the control (NTC) embryos. In addition, and unlike the NTC embryos, the treated embryos displayed a global acetylated histone H4 at lysine 8 profile similar to the in vitro-fertilized (IVF) and cultured embryos during the preimplantation development. Finally, we determined that several transcription factors exert a dramatic amount of genetic control over pluripotency, including Oct4, Nanog, Cdx2, and Rex01, the imprinting genes Igf2 and Igf2r, and the histone deacetyltransferase gene Hdac2. The NT blastocysts showed similar levels of Oct4, Cdx2, and Hdac2 but lower levels of Nanog than those of the IVF blastocyst. However, the NTTSA blastocysts showed similar levels of Rex01, Igf2, and Igf2r as those of IVF blastocysts, whereas the NTC blastocysts showed significantly lower levels for those genes. Our results suggest that TSA improves porcine SCNT preimplantation development and affects the acetylated status of the H4K8, rendering acetylation levels similar to those of the IVF counterparts.",

keywords = "Acetylation, Histones, Nucleus transfer, Reprogramming, Trichostatin A",

author = "Cervera, {R. P.} and N. Mart{\'i}-Guti{\'e}rrez and E. Escorihuela and R. Moreno and M. Stojkovic",

note = "Funding Information: This work was supported by funds for research in the field of regenerative medicine from the Regional Government Health Department (Generalitat Valenciana, Spain). The authors would like to thank the Mercavalencia Abattoir for their assistance in obtaining porcine ovaries. The confocal microscopy imaging was performed by the Confocal Microscopy Service of the “Centro de Investigaci{\'o}n Pr{\'i}ncipe Felipe.” We would like to thank Miguel Angel Silvestre and Michael John Reinhold for critical reading of the manuscript. ",

year = "2009",

month = nov,

doi = "10.1016/j.theriogenology.2009.06.030",

language = "English (US)",

volume = "72",

pages = "1097--1110",

journal = "Theriogenology",

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T1 - Trichostatin A affects histone acetylation and gene expression in porcine somatic cell nucleus transfer embryos

AU - Cervera, R. P.

AU - Martí-Gutiérrez, N.

AU - Escorihuela, E.

AU - Moreno, R.

AU - Stojkovic, M.

N1 - Funding Information: This work was supported by funds for research in the field of regenerative medicine from the Regional Government Health Department (Generalitat Valenciana, Spain). The authors would like to thank the Mercavalencia Abattoir for their assistance in obtaining porcine ovaries. The confocal microscopy imaging was performed by the Confocal Microscopy Service of the “Centro de Investigación Príncipe Felipe.” We would like to thank Miguel Angel Silvestre and Michael John Reinhold for critical reading of the manuscript.

PY - 2009/11

Y1 - 2009/11

N2 - Epigenetic aberrancies likely preclude correct and complete nuclear reprogramming after somatic cell nucleus transfer (SCNT) and may underlie the observed reduced viability of cloned embryos. In the current study, we tested the effects of the histone deacetylase-inhibitor trichostatin A (TSA) on preimplantation development and on histone acetylation and the gene expression of nucleus transfer (NT) porcine (Sus scrofa) embryos. Our results showed that 5 nM TSA for 26 h after reconstitution resulted in embryos (NTTSA) that reached the blastocyst stage at a higher level (48.1% vs. 20.2%) and increased number of cells (105.0 vs. 75.3) than that of the control (NTC) embryos. In addition, and unlike the NTC embryos, the treated embryos displayed a global acetylated histone H4 at lysine 8 profile similar to the in vitro-fertilized (IVF) and cultured embryos during the preimplantation development. Finally, we determined that several transcription factors exert a dramatic amount of genetic control over pluripotency, including Oct4, Nanog, Cdx2, and Rex01, the imprinting genes Igf2 and Igf2r, and the histone deacetyltransferase gene Hdac2. The NT blastocysts showed similar levels of Oct4, Cdx2, and Hdac2 but lower levels of Nanog than those of the IVF blastocyst. However, the NTTSA blastocysts showed similar levels of Rex01, Igf2, and Igf2r as those of IVF blastocysts, whereas the NTC blastocysts showed significantly lower levels for those genes. Our results suggest that TSA improves porcine SCNT preimplantation development and affects the acetylated status of the H4K8, rendering acetylation levels similar to those of the IVF counterparts.

AB - Epigenetic aberrancies likely preclude correct and complete nuclear reprogramming after somatic cell nucleus transfer (SCNT) and may underlie the observed reduced viability of cloned embryos. In the current study, we tested the effects of the histone deacetylase-inhibitor trichostatin A (TSA) on preimplantation development and on histone acetylation and the gene expression of nucleus transfer (NT) porcine (Sus scrofa) embryos. Our results showed that 5 nM TSA for 26 h after reconstitution resulted in embryos (NTTSA) that reached the blastocyst stage at a higher level (48.1% vs. 20.2%) and increased number of cells (105.0 vs. 75.3) than that of the control (NTC) embryos. In addition, and unlike the NTC embryos, the treated embryos displayed a global acetylated histone H4 at lysine 8 profile similar to the in vitro-fertilized (IVF) and cultured embryos during the preimplantation development. Finally, we determined that several transcription factors exert a dramatic amount of genetic control over pluripotency, including Oct4, Nanog, Cdx2, and Rex01, the imprinting genes Igf2 and Igf2r, and the histone deacetyltransferase gene Hdac2. The NT blastocysts showed similar levels of Oct4, Cdx2, and Hdac2 but lower levels of Nanog than those of the IVF blastocyst. However, the NTTSA blastocysts showed similar levels of Rex01, Igf2, and Igf2r as those of IVF blastocysts, whereas the NTC blastocysts showed significantly lower levels for those genes. Our results suggest that TSA improves porcine SCNT preimplantation development and affects the acetylated status of the H4K8, rendering acetylation levels similar to those of the IVF counterparts.

KW - Acetylation

KW - Histones

KW - Nucleus transfer

KW - Reprogramming

KW - Trichostatin A

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SN - 0093-691X

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JO - Theriogenology

JF - Theriogenology

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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