# Protein methylation pathways that control genetic susceptibility to environmental pollutants in the occurrence of craniofacial defects

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2022 · $422,376

## Abstract

PROJECT SUMMARY / ABSTRACT
Formation of the head and face is a complex process that is highly susceptible to disturbance as evidenced by
the high incidence of craniofacial birth defects. Dysregulation in genetic and environmental factors are the main
causes of craniofacial defects. However, less than 50% of craniofacial defect cases have identified genetic
causes, and mechanisms of gene-environment interaction remains poorly understood. Therefore, molecular
investigation is needed to increase understanding of craniofacial development. We recently identified a new
regulator of craniofacial morphogenesis that interacts with environmental stress. This regulator, Protein
Arginine Methyltransferase 1 (PRMT1), is an enzyme that methylates histone to generate a transcriptional
activation mark H4R3me2a and methylation non-histone proteins on arginine residues. Prmt1 ablation in
neural crest cells caused cleft palate and skull malformation. We further uncovered a role for PRMT1 in
guarding against environmental toxin TCDD-induced cleft palate. In this proposal, we aim to determine
PRMT1-dependent transcription and epigenetic mechanisms that regulated TCDD-induced cellular changes
and developmental defects, using mouse genetic models, biochemical and cell biology approaches, RNA-seq,
ChIP-seq and bioinformatic analysis.

## Key facts

- **NIH application ID:** 10436980
- **Project number:** 5R01DE030928-02
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Jian Xu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $422,376
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10436980

## Citation

> US National Institutes of Health, RePORTER application 10436980, Protein methylation pathways that control genetic susceptibility to environmental pollutants in the occurrence of craniofacial defects (5R01DE030928-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10436980. Licensed CC0.

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