# Improving Bovine Cloning Efficiency by Enhancing Reprogramming during Embryonic Genome Activation (EGA)

> **NIH NIH F32** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $71,430

## Abstract

This F32 proposal outlines research objectives to investigate the early gene expression regulation 
of bovine somatic cell nuclear transfer (SCNT) cloned embryos, and improve their developmental 
potential by harnessing our knowledge of IVF bovine preimplantation development. Based on several 
published reports, including my own work, my hypothesis is that failed embryonic genome activation 
(EGA) is the rate-limiting step negatively impacting the robust development of cloned animals. 
Because many EGA activated genes are involved in epigenetic reprogramming embryonic chromatin, 
failure to appropriately turn on these genes leads to developmental dysregulation and failure, 
often manifested much later in gestation.
Building upon both our published work, showing that DUX transcription factors (TF) are the master 
regulators of gene expression at the egg-to-embryo transition, and utilizing my extensive 
unpublished preliminary data laying the ground work for our hypothesis in the bovine system, I will 
first address this problem using cutting-edge genomic, epigenomic, and embryological methods. 
First, I will test whether the putative enhancer regions I identified in IVF bovine embryos show 
stage-specific transcriptional activity in vivo. I will also dissect which TFs the putative 
enhancer regions are responsive to using a cellular system. Then I will identify open chromatin 
regions in bovine SCNT embryos and compare them to the high-quality IVF embryo open chromatin maps 
I have previously generated. This will help me understand how much of the SCNT developmental 
phenotype is caused by failure to activate EGA chromatin or failure to decommission somatic cell 
open chromatin. Finally, I will use our data that cow DUXC is a major activator of bovine EGA to 
test our hypothesis that DUXC deficiency can be overcome by ectopically expressing DUXC in SCNT 
embryos and that this will increase the efficiency of SCNT. With significance for human assisted 
reproductive technologies, development of large animal models of human embryogenesis, agricultural 
significance of cloning, and ecological impacts of endangered species preservation through SCNT, 
this work integrates innovative strategies to impact multiple fields.

## Key facts

- **NIH application ID:** 9923462
- **Project number:** 5F32HD094500-03
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Edward J Grow
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $71,430
- **Award type:** 5
- **Project period:** 2018-05-01 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9923462

## Citation

> US National Institutes of Health, RePORTER application 9923462, Improving Bovine Cloning Efficiency by Enhancing Reprogramming during Embryonic Genome Activation (EGA) (5F32HD094500-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9923462. Licensed CC0.

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