# Enhancer activation mechanisms in cranial neural crest osteoblast differentiation

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $360,112

## Abstract

Project Summary
Enhancers play a vital role in initiating and maintaining expression of cell specific transcriptional programs. A
key feature in enhancer activation and gene regulation is changing the local chromatin state to facilitate binding
of transcriptional co-regulators to enhancers. Chromatin-modifying enzymes that are associated with enhancer
function are commonly mutated in human craniofacial disorders including histone methylases, demethylases,
acetylases, chromatin readers, and chromatin remodeling proteins. Many of these chromatin-modifying factors
biochemically associate and may co-regulate enhancer and transcriptional activation events within neural
crest, stem cells from which anterior facial bone and cartilage are derived. We have modeled several of these
human craniofacial disorders through tissue specific knockout of chromatin-modifying factors in mouse neural
crest cells. The experiments outlined in this proposal will characterize de novo enhancer activation by
chromatin profiling of primary cranial neural crest cells undergoing osteoblast differentiation. Neural crest cells
deficient in chromatin-modifying machinery will be analyzed molecularly for disruption of enhancer chromatin
states and to identify cooperative functions between these factors. This proposal will utilize a combination of
biochemical, genetic, and low cell number genomic approaches to elucidate the role of chromatin-based
enhancer activation in craniofacial disorder pathogenesis.

## Key facts

- **NIH application ID:** 10475308
- **Project number:** 5R01DE030530-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Karl Bryan Shpargel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $360,112
- **Award type:** 5
- **Project period:** 2021-09-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10475308

## Citation

> US National Institutes of Health, RePORTER application 10475308, Enhancer activation mechanisms in cranial neural crest osteoblast differentiation (5R01DE030530-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10475308. Licensed CC0.

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