# Mechanisms controlling cell type-specific transcription factor activity in the development of serially homologous structures in Drosophila

> **NIH NIH F31** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $48,974

## Abstract

Project summary/abstract
To ensure proper morphogenesis and cell fate specification, animals must generate highly stereotyped spatial
and temporal patterns of gene expression. To this end, transcription factors (TFs) bind DNA regulatory
elements such as enhancers to activate or repress transcription in particular cell types at particular
developmental stages. Many TFs are expressed in several cell types at multiple stages throughout animal
development. These TFs modulate different gene regulatory networks (GRNs) in different cell types, allowing a
single TF to specify multiple cell fates. Despite decades of research, it remains unclear how individual TFs are
able to perform distinct functions in different cell types. One example of such a TF is the Drosophila Hox TF
Ultrabithorax (Ubx). Ubx specifies third thoracic (T3) segmental identity by binding thousands of enhancers to
regulate hundreds of genes, modifying the ground-state second thoracic segment (T2) GRN. T3 is highly
modified at all positions along the proximal-distal (PD) axis relative to the serially homologous T2, including
morphological changes to the body wall, hinge, and appendage proper. All of these changes must ultimately
be due to Ubx activity. A primary mechanism by which TFs such as Ubx enact changes in GRNs is through
modification of chromatin structure. This is largely mediated by TF interaction with chromatin remodeling
enzymes, leading to histone post-translational modifications and changes in chromatin accessibility at
targeted genomic loci. My proposal outlines a series of experiments to identify cell type-specific molecular
interactions that underlie cell type-specific Ubx binding, chromatin-modifying activities, and transcriptional
regulatory activities. Recent evidence from our lab suggests that Ubx chromatin remodeling activity is
spatially segregated along the PD axis in T3. In Aim 1 of my Research Strategy, I will test the hypothesis that
Ubx functions predominantly to either promote a more open chromatin state in intermediate positions along
the PD axis or a more closed chromatin state in proximal and distal positions along the PD axis. I will use a
novel technique developed in our lab called SpyChIP to assay Ubx binding in these distinct populations of
cells along the PD axis in T3. I will also perform ATAC-seq in these populations to identify changes in
chromatin accessibility downstream of Ubx binding. These experiments will provide information as to how TF
binding leads to differential chromatin landscapes in different populations of cells. In Aim 2, I will test the
hypothesis that the zinc finger TF Teashirt (Teashirt) mediates Ubx repressive activity in the proximal domain
of T3. In this Aim, I describe both gain- and loss-of-function experiments to characterize the role of Tsh in
regulating Ubx repressive activity. I will also perform protein-protein interaction experiments to determine if
Ubx interacts with Tsh and other coregulators in a cell type-specific manner. Over...

## Key facts

- **NIH application ID:** 11099655
- **Project number:** 5F31HD110242-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Ross Munce
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 5
- **Project period:** 2023-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11099655

## Citation

> US National Institutes of Health, RePORTER application 11099655, Mechanisms controlling cell type-specific transcription factor activity in the development of serially homologous structures in Drosophila (5F31HD110242-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11099655. Licensed CC0.

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