# Transcriptional control of Hedgehog/Gli target enhancers

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $339,556

## Abstract

Abstract
Cell-cell signaling pathways control the fate of cells during development and in adult stem cell
contexts, and are frequently mis-regulated in disease states. Hedgehog, an ancient and highly
conserved signaling pathway with many roles in animal development and homeostasis, controls
the activity of Gli transcription factors, which then bind to sites within enhancers, or cis-
regulatory elements, in the genome to influence the transcription of pathway target genes.
Enhancers integrate spatial, temporal, physiological, and lineage information to control the
pattern, timing, and levels of gene expression. Enhancer sequences account for a large
proportion of disease-associated genomic variation in human populations. Investigating the
mechanisms by which signal-regulated enhancers control gene expression helps us understand
how organisms, tissues, and organs self-assemble during development, how they are
maintained in adulthood, how they go awry in disease, and how new features are acquired and
modified in the course of evolution. New tools for studying gene regulation at a detailed,
mechanistic level have been developed over the past several years: these tools, combined with
more established experimental approaches, provide opportunities to ask fundamental questions
about how the regulatory genome functions and evolves.
This highly collaborative project takes advantage of the remarkable conservation of the
Hedgehog/Gli pathway with a multi-organismal approach, focusing on regulatory mechanisms
that are common to fruit fly, chick, and mouse development, and benefiting from the
experimental strengths of each of these model systems. The proposed project will combine fly
and vertebrate model systems to accomplish three objectives: (1) Determine how Gli binding
motifs in DNA, and common Gli motif variants, control the expression of Hedgehog target
genes; (2) Investigate competition for occupancy of Gli binding motifs as a transcriptional
regulatory mechanism; and (3) Decode the cis-regulatory logic of developmental Hedgehog/Gli
target enhancers in flies and vertebrates.

## Key facts

- **NIH application ID:** 9923721
- **Project number:** 5R01GM124251-04
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Scott Barolo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $339,556
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9923721

## Citation

> US National Institutes of Health, RePORTER application 9923721, Transcriptional control of Hedgehog/Gli target enhancers (5R01GM124251-04). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9923721. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*