# Trichostatin A-Induced Epigenetic Modifications and Their Influence on the Development of Porcine Cloned Embryos Derived from Bone Marrow–Mesenchymal Stem Cells

**Authors:** Seung-Chan Lee, Won-Jae Lee, Young-Bum Son, Yeung Bae Jin, Hyeon-Jeong Lee, Eunyeong Bok, Sangyeob Lee, Sang-Yun Lee, Chan-Hee Jo, Tae-Seok Kim, Chae-Yeon Hong, Seo-Yoon Kang, Gyu-Jin Rho, Yong-Ho Choe, Sung-Lim Lee

PMC · DOI: 10.3390/ijms26052359 · International Journal of Molecular Sciences · 2025-03-06

## TL;DR

This study shows that Trichostatin A improves the development of cloned pig embryos by altering epigenetic markers and gene expression.

## Contribution

The study reveals how TSA affects histone acetylation and gene expression in cloned embryos from mesenchymal stem cells.

## Key findings

- TSA treatment increased blastocyst formation in cloned embryos from 13.7% to 32.5%.
- TSA elevated the expression of CDX2, NANOG, and IGF2R in cloned embryos.
- TSA increased acH3K9 and acH3K18 fluorescence but not acH4K12 levels during early development.

## Abstract

Abnormal epigenetic reprogramming of nuclear-transferred (NT) embryos leads to the limited efficiency of producing cloned animals. Trichostatin A (TSA), a histone deacetylase inhibitor, improves NT embryo development, but its role in histone acetylation in porcine embryos cloned with mesenchymal stem cells (MSCs) is not fully understood. This study aimed to compare the effects of TSA on embryo development, histone acetylation patterns, and key epigenetic-related genes between in vitro fertilization (IVF), NT-MSC, and 40 nM TSA-treated NT-MSC (T-NT-MSC). The results demonstrated an increase in the blastocyst rate from 13.7% to 32.5% in the T-NT-MSC, and the transcription levels of CDX2, NANOG, and IGF2R were significantly elevated in T-NT-MSC compared to NT-MSC. TSA treatment also led to increased fluorescence intensity of acH3K9 and acH3K18 during early embryo development but did not differ in acH4K12 levels. The expression of epigenetic-related genes (HDAC1, HDAC2, CBP, p300, DNMT3a, and DNMT1) in early pre-implantation embryos followed a pattern similar to IVF embryos. In conclusion, TSA treatment improves the in vitro development of porcine embryos cloned with MSCs by increasing histone acetylation, modifying chromatin structure, and enhancing the expression of key genes, resulting in profiles similar to those of IVF embryos.

## Linked entities

- **Genes:** CDX2 (caudal type homeobox 2) [NCBI Gene 1045], NANOG (Nanog homeobox) [NCBI Gene 79923], IGF2R (insulin like growth factor 2 receptor) [NCBI Gene 3482], HDAC1 (histone deacetylase 1) [NCBI Gene 3065], HDAC2 (histone deacetylase 2) [NCBI Gene 3066], CREBBP (CREB binding lysine acetyltransferase) [NCBI Gene 1387], EP300 (EP300 lysine acetyltransferase) [NCBI Gene 2033], DNMT3A (DNA methyltransferase 3 alpha) [NCBI Gene 1788], DNMT1 (DNA methyltransferase 1) [NCBI Gene 1786]
- **Chemicals:** Trichostatin A (PubChem CID 444732)

## Full-text entities

- **Genes:** IGF2R (insulin like growth factor 2 receptor) [NCBI Gene 3482] {aka CD222, CI-M6PR, CIMPR, M6P-R, M6P/IGF2R, MPR 300}, CDX2 (caudal type homeobox 2) [NCBI Gene 1045] {aka CDX-3, CDX2/AS, CDX3}, HDAC1 (histone deacetylase 1) [NCBI Gene 3065] {aka GON-10, HD1, KDAC1, RPD3, RPD3L1}, NANOG (Nanog homeobox) [NCBI Gene 79923], CREBBP (CREB binding lysine acetyltransferase) [NCBI Gene 1387] {aka CBP, KAT3A, MKHK1, RSTS, RSTS1}, EP300 (EP300 lysine acetyltransferase) [NCBI Gene 2033] {aka KAT3B, MKHK2, RSTS2, p300}, DNMT3A (DNA methyltransferase 3 alpha) [NCBI Gene 1788] {aka DNMT3A2, HESJAS, M.HsaIIIA, TBRS}, HDAC2 (histone deacetylase 2) [NCBI Gene 3066] {aka HD2, KDAC2, RPD3, YAF1}, DNMT1 (DNA methyltransferase 1) [NCBI Gene 1786] {aka ADCADN, AIM, CXXC9, DNMT, HSN1E, MCMT}

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC11900109/full.md

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11900109/full.md

## References

43 references — full list in the complete paper: https://tomesphere.com/paper/PMC11900109/full.md

---
Source: https://tomesphere.com/paper/PMC11900109