# Overexpression of the pioneer transcription factor Nr5a2 promotes the development of mouse somatic cell nuclear transfer embryos

## TL;DR

Overexpressing the Nr5a2 transcription factor improves the development of mouse embryos created through somatic cell nuclear transfer.

## Contribution

The study shows that Nr5a2 overexpression enhances SCNT efficiency by improving genome activation and transcriptional activity.

## Key findings

- Nr5a2 overexpression improves zygotic genome activation in SCNT embryos.
- It enhances the morula-to-blastocyst transition and increases birth rates.
- Nr5a2 recruits P300 to increase H3K27ac at low-expression genes, restoring transcription.

## Abstract

Somatic cell nuclear transfer (SCNT) is a valuable tool in regenerative medicine, yet its efficiency remains limited by epigenetic reprogramming barriers that have been partially corrected by global regulation of epigenetic enzymes. However, these approaches lack gene locus specificity and may disrupt normal gene regulation. Therefore, new strategies capable of broadly enhancing reprogramming fidelity are needed. Here, we demonstrate that overexpression of the pioneer transcription factor Nr5a2 in mouse SCNT embryos improves both zygotic genome activation and the morula-to-blastocyst transition, two major developmental barriers in SCNT, and enhances birth rates. Mechanistically, Nr5a2 recruits P300 to increase H3K27ac at genes with low expression, restoring transcriptional activity and promoting SCNT embryo development.

Somatic Cell Nuclear Transfer (SCNT) is an approach that enables the generation of an embryo from a somatic cell, but its efficiency remains low due to epigenetic barriers. This study shows that pioneer transcription factor Nr5a2 overexpression enhances SCNT embryo development by improving genome activation and recruiting P300 to restore transcriptional activity.