# Probing the activity of DUX4 in FSHD

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2021 · $521,846

## Abstract

Abstract
FSHD affects over 25,000 individuals in the United States. It is the third most common muscular dystrophy by
incidence but may be the most common by prevalence (Orphanet, 2008). The DNA lesion associated with this
disease is a contraction within a series of 3.3 kb repeats (D4Z4 repeats) near the telomere of 4q. The
contraction modifies the chromatin configuration of 4q35.2 which results in misexpression of a gene encoded
within each D4Z4 repeat, DUX4. We have shown that DUX4 is cytotoxic when expressed at high levels in
various cellular model systems, and interferes with myogenic gene expression when expressed at low levels in
satellite cells and myoblasts, and have generated an animal model that recapitulates one key aspect of the
human disease: muscle deterioration in the presence of barely-detectable DUX4 protein. However
mechanistically, DUX4 is still not well understood, we do not have a clear picture of which cell types in muscle
express DUX4 and what the consequence of that expression is, a pathological mechanism explaining muscle
loss still eludes the field, and we suffer from a dearth of specific therapies for FSHD. The research proposed in
this application addresses these issues by (1) probing the mechanism of DUX4-mediated transcription,
including studying inhibitors of that transcription (2) investigating the effects of inhibiting the p300 pathway
genetically and pharmacologically in the mouse model, and (3) studying DUX4 expression in primary cells from
FSHD patients. This research will address key outstanding questions in FSHD, will advance a mechanistic
understanding of DUX4 in FSHD at the molecular, cellular, and tissue levels, and may lead to new therapeutic
directions.

## Key facts

- **NIH application ID:** 10240733
- **Project number:** 5R01AR055685-12
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Michael Kyba
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $521,846
- **Award type:** 5
- **Project period:** 2010-03-19 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10240733

## Citation

> US National Institutes of Health, RePORTER application 10240733, Probing the activity of DUX4 in FSHD (5R01AR055685-12). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10240733. Licensed CC0.

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