# Mechanisms of Cu-binding factors to promote myogenic gene expression

> **NIH NIH R01** · WESLEYAN UNIVERSITY · 2021 · $361,460

## Abstract

PROJECT SUMMARY
 Cell development and differentiation require lineage specific mechanisms by which cells initiate programs
of gene expression. In normal conditions, lineage determination involves activation of genes that are
transcriptionally silent by specific transcription factors, chromatin remodelers, coactivators, and other lineage
specific molecules. Skeletal muscle differentiation is an excellent model for studying fundamental principles of
tissue-specific gene expression and differentiation as there is a significant understanding of mechanisms
controlling myogenic-specific gene expression. However, emerging evidence shows a novel category of
Copper (Cu)-binding factors that may have a previously unappreciated direct impact in the regulation of
myoblast proliferation and differentiation.
 Cu is an essential trace metal that serves as a catalytic co-factor for a wide variety of enzymatic reactions
that play critical roles in life. Cu deficiency and overload leads to pathophysiological conditions including
Menkes and Wilson’s diseases, neutropenia, impaired iron absorption, peripheral neuropathy, mitochondrial
deficiencies and hypertrophic cardiomyopathy. Therefore, the mechanisms for Cu distribution and usage in
different tissues and organs, as well as the consequences due to dysregulated Cu acquisition, are important to
human health. Limited information is available regarding Cu and Cu-binding factors and their mechanisms of
action in myogenesis and most developmental processes. We propose to elucidate novel mechanisms of gene
regulation that drive muscle differentiation and development and that are dependent on copper and Cu-binding
transcription factors. We propose integrative studies that combine diverse molecular, biochemical and
spectroscopic techniques to characterize novel molecular mechanisms by which Cu-binding factors regulate
myogenic differentiation. We propose a novel model where Cu controls myogenesis by activating Cu-TFs that
may act synchronously, either by acting on different promoters at the same time or by acting sequentially at
different stages of differentiation, or both. Our experiments will identify new components and mechanisms for
mammalian Cu-binding factors in the regulation of lineage-specific gene expression. Our studies also will
establish a basis for understanding muscular diseases related to aberrant Cu biology using well-characterized
mouse models for Menkes and Wilson’s diseases. Understanding the molecular mechanisms that drive lineage
specific gene expression dependent on Cu will greatly advance our knowledge of several Cu-related diseases.

## Key facts

- **NIH application ID:** 10209843
- **Project number:** 1R01AR077578-01A1
- **Recipient organization:** WESLEYAN UNIVERSITY
- **Principal Investigator:** Teresita Del Nino Jesus Padilla-Benavides
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $361,460
- **Award type:** 1
- **Project period:** 2021-08-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10209843

## Citation

> US National Institutes of Health, RePORTER application 10209843, Mechanisms of Cu-binding factors to promote myogenic gene expression (1R01AR077578-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10209843. Licensed CC0.

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