# Determinants of Context Specific Transcription Factor Function

> **NIH NIH F31** · EMORY UNIVERSITY · 2022 · $46,752

## Abstract

Project Summary:
The developing embryo relies on gene expression to be orchestrated on strict temporal and quantitative levels.
Without proper coordination, the zygote suffers severe consequences such as growth issues and even embryo
termination. Early embryonic gene regulation is carried out by maternally deposited transcription factors which
are able to find their cognate cis sequences and activate the zygotic genome with tremendous efficacy despite
the crowded environment of the nucleus. Once correctly targeted, transcription factors can perform context-
specific functions across the genome even while sharing similar cis element sequence structure. I aim to define
the relationship between transcription factors and their cis sequences by asking what are the contributions of
DNA sequence and genomic context to transcription factor function in the early embryo? I will use the
excellent genetic model system Drosophila melanogaster to investigate context-specific functions of the
maternally deposited transcription factor Chromatin-Linked Adapter for MSL Proteins (CLAMP). CLAMP
targets GA-rich cis elements in the embryonic genome, but performs several distinct functions depending on
genomic context. For example, CLAMP primes the male X-chromosome for dosage compensation, regulates
promoters genome-wide, and promotes formation of the conserved histone locus body (HLB), which regulates
developmental and cell cycle expression of the replication-dependent histone genes. CLAMP targeting occurs
in the embryo and when CLAMP is depleted, embryos terminate before the zygotic genome is activated. Although
CLAMP targets similar cis elements in all three contexts, it recruits very different locus-specific transcription
factors. I hypothesize that CLAMP inputs both DNA sequence information and genomic context to perform its
context-specific functions. In Aim 1, I will engineer fly lines carrying a transgenic histone locus in which I have
replaced the natural cis elements with CLAMP-recruiting GA-rich elements from different genomic origins. I will
assess how these cis elements impact early embryo HLB formation, CLAMP binding, and histone gene
transcription to determine how similar cis elements from different origins impact CLAMP function. In Aim 2, I will
perform (A) in vitro gel-shift assays and (B) in vivo experiments, in which I vary the length of the CLAMP-recruiting
cis elements and determine binding affinity and transcriptional output. In this aim, I will determine the contribution
of cis element affinity to transcription factor function. Overall, the proposed aims will define how cis element DNA
sequence and genomic context influence context-specific transcription factor function in the early embryo.

## Key facts

- **NIH application ID:** 10462505
- **Project number:** 5F31HD105452-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Lauren Jessica Hodkinson
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 5
- **Project period:** 2021-09-15 → 2024-09-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10462505

## Citation

> US National Institutes of Health, RePORTER application 10462505, Determinants of Context Specific Transcription Factor Function (5F31HD105452-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10462505. Licensed CC0.

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