# Establishment of Active Chromatin Domains

> **NIH NIH R35** · BROWN UNIVERSITY · 2022 · $398,678

## Abstract

Chromatin domains form within the nucleus during early development to precisely 
co-regulate nearby genes during the maternal to zygotic transition. Prior to zygotic 
genome activation, the entire genome is very open and only a few key early transcription 
factors are bound. Yet, many essential active and repressive chromatin domains are present right 
 after zygotic genome activation. Little is understood about how embryos rapidly 
establish the critical active chromatin domains that are essential for the function of the zygotic 
genome.
Here are several key questions about active chromatin domains that we will address in this 
proposal:

1) How are different effector complexes specifically targeted to active chromatin domains 
 by similar
cis-elements such that the proper domain forms at the correct genomic location?
2) How does competition between transcription factors that recognize similar cis-elements regulate 
the formation of active chromatin domains during development?
3) How is the three-dimensional architecture of active chromatin domains established?

There are many essential chromatin domains that mediate coordinate gene activation throughout the 
genome including the rDNA locus, the histone locus and the dosage compensated male 
X-chromosome, all of which must be properly activated in the developing embryo. My 
research program has initially focused on two of these essential chromatin domains of 
coordinate gene activation in Drosophila: 1) the dosage compensated X-chromosome that balances 
gene dosage between sexes and 2) the histone locus body (HLB) that coordinately 
regulates histone gene expression. Drosophila is an ideal organism with which to study 
the formation of chromatin domains early in development due to their rapid and synchronized early 
development and the large number of genetic and biochemical tools and genomic data sets available.
While many cis and trans acting factors that regulate chromatin domains have been identified, 
little is known about the molecular mechanisms that drive their formation at specific genomic loci 
during early development. Defining how the chromatin domains on the active male 
X-chromosome and the HLB are established and maintained over developmental time will reveal 
key principles by which active chromatin domains form. Using steady-state measurements, we have 
recently discovered that a single transcription factor, CLAMP, regulates formation of both the 
dosage compensated X-chromosome and the HLB active chromatin domains, providing us an entry 
point for revealing new insights into the dynamic process of chromatin domain 
formation. The significance of our work is that we will define how active chromatin domains form 
over developmental time and will seek to identify common underlying mechanisms that drive 
 formation of two very different domains at specific genomic loci.

## Key facts

- **NIH application ID:** 10373015
- **Project number:** 5R35GM126994-05
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Erica Nicole Larschan
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $398,678
- **Award type:** 5
- **Project period:** 2018-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10373015

## Citation

> US National Institutes of Health, RePORTER application 10373015, Establishment of Active Chromatin Domains (5R35GM126994-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10373015. Licensed CC0.

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