# Defining the molecular interactions that drive histone locus body formation and function

> **NIH NIH F32** · EMORY UNIVERSITY · 2022 · $67,582

## Abstract

PROJECT SUMMARY
 Eukaryotic nuclei are crowded compartments that not only compact but also organize meters of DNA.
This feat is achieved by wrapping DNA around histone proteins to form nucleosomes, the basic units of
chromatin. Histone levels in the cell are precisely balanced: a lack of histone expression causes cell cycle arrest,
whereas histone overexpression leads to genomic instability. Although histone gene regulation is crucial for
proper cell viability and function, mechanisms that regulate histone gene expression are poorly defined.
 Histone genes are often clustered in metazoan genomes. In the genome of the excellent model system
Drosophila melanogaster, a single cluster encompasses all the canonical histone genes. A suite of transcription
and processing factors occupy the histone gene locus and form a conserved structure known as the histone
locus body (HLB). Mutations in known HLB members lead to defects in HLB formation and/or histone gene
expression, often causing animal lethality or infertility. We do not know all the factors that occupy the histone
locus and contribute to histone gene regulation, and there are large gaps in our understanding of how HLB
factors specifically target the histone gene locus. The overall goal of this proposal is to define the molecular
interactions at the histone locus that specify histone genes for unique regulation.
 Recent studies identified the Drosophila protein CLAMP, which binds specifically to GA-repeat
sequences within the histone3/histone4 promoter, opens chromatin across the histone locus, and promotes
expression of all histone genes. However, it is unclear if CLAMP is required at the histone locus prior to the
localization of HLB-specific factors, which would implicate CLAMP in specifying the locus for HLB formation. In
Aim 1, I will define the DNA-protein interactions that lead to HLB formation and histone gene expression. I will
take advantage of an established transgenic histone locus system to (A) probe the positional requirements of
the CLAMP-GA-repeat interaction and (B) determine the placement of CLAMP in the developmental hierarchy
of HLB formation. It is also critical that we define HLB composition, as this is an important step towards defining
mechanisms of HLB formation and histone gene regulation. In Aim 2, I will discover novel HLB factors using
both an unbiased proteomic screen and a candidate approach that involves mining existing -omics datasets.
This candidate approach will also be the basis of a Course-Based Undergraduate Research Experience (CURE)
module that I will develop and utilize in both my future independent laboratory and classroom. Collectively, these
experiments will define mechanisms of HLB formation and histone gene expression while expanding my
experimental repertoire and generating new directions for my future laboratory and classroom.

## Key facts

- **NIH application ID:** 10464621
- **Project number:** 1F32GM140778-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Casey Alexandra Schmidt
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $67,582
- **Award type:** 1
- **Project period:** 2022-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10464621

## Citation

> US National Institutes of Health, RePORTER application 10464621, Defining the molecular interactions that drive histone locus body formation and function (1F32GM140778-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10464621. Licensed CC0.

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