# Chromatin Transitions during Early Embryonic Development in Drosophila melanogaster

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2021 · $375,750

## Abstract

PROJECT SUMMARY
 Genetic inheritance material of a living organism (DNA) is stored in chromosomes. Understanding of
cellular activities in normal development and disease requires more than the DNA sequence and individual-
specific variations of the genome. Critical regulatory roles are also played by packaging of the genome into a
conserved nucleoprotein complex termed chromatin. The structure of chromatin and the regulatory
machinery of its metabolism are uniquely important and thus, strongly conserved in evolution.
 The ultimate objective of our work is to understand the relationship between the establishment of
chromatin structure and regulation of the function of eukaryotic chromosomes. We will focus on a
systematic study of proteins that mediate chromatin assembly and remodeling in the embryo of a model
organism, fruit fly (Drosophila melanogaster). We will examine how the activities of histone chaperones
and motor factors mediate chromatin assembly in vitro (in a test tube) and investigate their specific
functional roles in vivo (in a living organism).
 Initially, the paternal DNA is presented to a fertilized egg as a specialized nucleoprotein complex. Sperm
chromatin differs in composition and structure from the normal cell chromatin, in particular by an
extraordinary high degree of DNA condensation. It is enzymatically static and is formed by compaction of
DNA with small basic, cysteine-rich proteins termed protamines. Despite its importance for the life cycle of
any sexually reproducing organism, sperm chromatin structure has been poorly studied. To fill this gap, we
will perform biochemical, biophysical and structural analyses of in vitro reconstituted Drosophila sperm
chromatin.
 At fertilization, the egg faces the challenge of remodeling the condensed sperm chromatin into an
accessible, transcription- and replication-competent form. We recently discovered cellular machinery that
mediates sperm chromatin remodeling in vitro and in vivo. Thus, we will also study the factors (protamine
chaperones and enzymes of the thioredoxin system) that mediate sperm chromatin remodeling.
 The successful completion of this project will lead to a comprehensive biochemical and biological
characterization of factors that mediate the assembly of various forms of chromatin. More globally, our work
will provide insights into the role of chromosome assembly and maintenance in regulation of the cell
function and will be applicable to understanding, diagnosis and treatment of human diseases that involve
defects in processes of DNA metabolism.

## Key facts

- **NIH application ID:** 10246982
- **Project number:** 5R01GM074233-18
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** DMITRY V FYODOROV
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $375,750
- **Award type:** 5
- **Project period:** 2005-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246982

## Citation

> US National Institutes of Health, RePORTER application 10246982, Chromatin Transitions during Early Embryonic Development in Drosophila melanogaster (5R01GM074233-18). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10246982. Licensed CC0.

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