# Molecular mechanisms of the maternal to zygotic transition

> **NIH NIH R35** · YALE UNIVERSITY · 2024 · $99,535

## Abstract

SUMMARY
The maternal to zygotic transition is a universal step in animal development characterized by the
clearance of the maternally provided mRNAs and the activation of the zygotic genome. These two
processes are intimately interconnected, as maternal factors drive the activation of the zygotic genes,
and zygotic products actively target maternal mRNAs for deadenylation, repression and clearance.
While recent studies have begun to identify individual factors that regulate mRNA stability and
activation of the zygotic genome, we lack major understanding of 1) the regulatory code (sequences,
structures and readers) that shapes genome activation and post-transcriptional regulation, 2) the
mechanisms that regulate genome activation and protein output, and 3) how different regulatory
mechanisms are integrated to instruct mRNA turnover, translation regulation and genome activation in
the embryo. The overarching project combines massive parallel reporter assays to determine the
regulatory activity of different sequences in the early embryo, protein interaction maps (at the level of
the DNA and RNA) to define the factors that mediate transcriptional and post-transcriptional regulation,
and novel imaging approaches to determine how pioneer factors shape chromatin structure and, in
turn, genome activation. Together these experiments will define the mechanisms that trigger each of
these steps in vivo and the gene regulatory network that controls early vertebrate development.
This project is relevant for public health across different contexts. First, from the standpoint of human
disease and cancer, pathways that control mRNA stability play an important role in aberrant oncogene
activation in cancer and are relevant to changes in cell fate where the cells transition to a new program
and remove the previous one through post-transcriptional regulation. Second, from the standpoint of
reproductive health, infertility is estimated to affect 15% of reproductive aged women, and early
pregnancy loss occurs in 25% of all pregnancies and up to 70% of pregnancies after in vitro fertilization.
Understanding the mechanisms of zygotic genome activation and maternal mRNA decay can provide
fundamental insights into human infertility and the development of tools to evaluate early loss of
fertilized eggs.
The results from this project will help us understand how gene expression is regulated in the early
embryo to trigger the activation of different developmental pathways during embryogenesis, and more
generally, will have broad implications in the study of genome activation and changes in cell fate.

## Key facts

- **NIH application ID:** 11036445
- **Project number:** 3R35GM122580-07S1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Antonio J Giraldez
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $99,535
- **Award type:** 3
- **Project period:** 2024-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11036445

## Citation

> US National Institutes of Health, RePORTER application 11036445, Molecular mechanisms of the maternal to zygotic transition (3R35GM122580-07S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11036445. Licensed CC0.

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