# Mechanisms of Nuclear Body Formation in the Early Embryo

> **NIH NIH R00** · EMORY UNIVERSITY · 2021 · $235,070

## Abstract

SUMMARY:
Coordinated gene regulation is especially critical in the developing embryo where the zygotic genome initiates
transcription for the first time. A conserved strategy to facilitate coordinated gene regulation is formation of
conserved structures called nuclear bodies, sub-nuclear regions at which specific factors accumulate to
perform regulatory and transcriptional functions. The histone locus body (HLB) is a conserved nuclear body
that regulates the histone genes, and I discovered that the zinc finger protein, CLAMP (Chromatin Linked
Adaptor for MSL Proteins), is essential to HLB regulation in Drosophila melanogaster. My research now aims
to address the key question: How does CLAMP act in a context-specific manner to initiate nuclear body
formation during the critical developmental stage of zygotic genome activation?
In Aim 1 of this project I will define the role of CLAMP in chromatin accessibility and factor recruitment during
zygotic genome activation. I will perform ATAC-seq and transcription factor ChIP-seq from sexed embryo pools
in the presence and absence of CLAMP, around the time point of zygotic genome activation. I will receive
mentorship from my mentor, Dr. Erica Larschan at Brown University. These experiments will address how
chromatin state affects nuclear body formation and how the composition of chromatin changes at ZGA when
nuclear bodies assume their unique properties. In Aim 2 I will use genetic tools to determine the developmental
timing requirements of CLAMP at the HLB and the specific qualities of cis-elements that allow HLB formation,
under mentorship from my co-mentor Dr. Robert Duronio at the University of North Carolina-Chapel Hill. This
aim will compare the mechanism(s) of HLB initiation and maintenance throughout development. In Aim 3 I will
perform Proteomics of Isolated Chromatin Segments in early embryos in the presence and absence of
CLAMP, followed by mass spectrometry analysis. I will identify unknown HLB components and their reliance
on CLAMP recruitment, under mentorship from my co-mentor Dr. Paul Schedl at Princeton University. This aim
will illuminate the mechanism of early embryonic nuclear body formation, including the ordered recruitment of
known and novel factors over developmental time.
I will perform the proposed experiments while also gaining experience and critical background in
developmental biology and proteomics. I will also develop my teaching and mentoring skills through hands on
experience and leadership/laboratory management courses. My proposed research will generate significant
new experimental directions, and my proposed career development will support me, as I initiate my
independent laboratory.

## Key facts

- **NIH application ID:** 10187613
- **Project number:** 5R00HD092625-05
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Leila Elizabeth Rieder
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $235,070
- **Award type:** 5
- **Project period:** 2019-07-18 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10187613

## Citation

> US National Institutes of Health, RePORTER application 10187613, Mechanisms of Nuclear Body Formation in the Early Embryo (5R00HD092625-05). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10187613. Licensed CC0.

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