# Metabolic control of global gene expression during the Maternal-to-Zygotic Transition

> **NIH NIH F32** · HARVARD MEDICAL SCHOOL · 2021 · $72,630

## Abstract

ABSTRACT
After an egg is fertilized, many thousands of genes are turned on in the embryo while maternal mRNA is
degraded; this process is called the maternal-to-zygotic transition (MZT). The goal of this proposal is to
decipher how activation of zygotic genes is synchronized with maternal mRNA decay. Both histone
modifications and the mRNA modification N6-methyladenosine (m6A) play prominent roles, during the MZT,
by regulating transcription of zygotic genes and maternal mRNA clearance, respectively. However, the signals
that control changes in chromatin and mRNA modifications in this critical developmental stage are largely
unknown. This proposal will test the novel hypothesis that changes in cellular metabolism coordinate global
gene expression during the MZT, through modulating the availability of metabolites required for chromatin
and mRNA modifications. Using high-resolution mass-spectrometry, in Drosophila (D). melanogaster
embryos during the MZT, we identified changes in the levels of alpha-ketoglutarate (α-KG), which is a required
co-factor for histone and RNA demethylation enzymes. Here, we test our central hypothesis through the
following specific aims: (1) test the link between α-KG levels, histone methylation, and global transcription
activation of zygotic genes, and (2) test the link between α-KG levels, m6A modification of mRNA, and
maternal mRNA decay. D. melanogaster embryos are an ideal system for studying the interplay between
metabolism and gene regulation because there are many experimental tools for manipulating and measuring
metabolism, chromatin state, mRNA modifications and transcription in vivo. This proposal will apply
molecular, genetic and genomic approaches to demonstrate how metabolic inputs, such as α-KG, shape the
developmental transcriptome and coordinate critical developmental processes by controlling both chromatin
and mRNA modifications. Findings from this study will be relevant for understanding not only developmental
processes but also diseases in which metabolic dysfunction is associated with abnormal gene expression, such
as cancer and diabetes. Establishing D. melanogaster as an experimental platform for studying metabolic
regulation of global gene expression and acquiring the relevant set of skills as part of this research plan will be
a critical next step towards fulfilling my goal of becoming an independent investigator.

## Key facts

- **NIH application ID:** 10074575
- **Project number:** 5F32HD095590-03
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Lital Bentovim
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $72,630
- **Award type:** 5
- **Project period:** 2019-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10074575

## Citation

> US National Institutes of Health, RePORTER application 10074575, Metabolic control of global gene expression during the Maternal-to-Zygotic Transition (5F32HD095590-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10074575. Licensed CC0.

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