# MYOD Regulation of 3D Chromatin Structure

> **NIH NIH R01** · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · 2020 · $390,000

## Abstract

PROJECT SUMMARY
This proposal aims at providing mechanistic insights into MYOD regulation of the high-order chromatin
interactions that define the 3D nuclear architecture of skeletal muscle cells, by capitalizing on the
unprecedented availability of high-resolution matrices of the genomic interactions induced by MYOD during
skeletal myogenesis from our preliminary studies. This study will fill a critical gap of basic knowledge in the
control of transcription and muscle stem cell biology, by exploring a higher level of complexity in the regulation
of gene expression in muscle satellite cells introduced by the spatial dimension. The Specific Aims are: Aim 1
Molecular analysis of MYOD-directed regulation of 3D chromatin structure in muscle progenitors. 1a To
determine the contribution of specific MYOD domains to structural and functional alterations of high-order
chromatin interactions that regulate gene expression. We will monitor the effect of MYOD mutants on 3D
chromatin structure and transcriptional output at specific loci. 1b To determine the role of co-factors in MYOD-
directed rewiring of chromatin interactions that regulate gene expression. We will investigate the role of
architectural proteins (CTCF and cohesin) as well as specific components of the chromatin-remodeling
complex and the transcriptional machinery - including BAF60C, Polymerase II (PolII), TAF3, Bromodomain and
Extra-Terminal Domain (BET) proteins - in MYOD-directed reconfiguration of chromatin interactions within
specific nuclear topological domains. 1c To investigate MYOD-directed control of high-order chromatin
interactions in satellite cells. We will determine the role of MYOD and co-factors on regulation of 3D chromatin
interactome and transcriptional output in satellite cells isolated from a mouse model of conditional genetic
ablation of MyoD. Aim 2 MYOD-directed regulation of 3D chromatin structure for signal-dependent
control of gene expression 2a. To functionally challenge MYOD-regulated cis-regulatory elements for signal-
regulated gene expression. We will exploit Cas9-based genome editing, RNAi-based knockdown and
pharmacological targeting of key epigenetic events to interrogate the dynamics of enhancer activation and
chromatin interactions in response to extrinsic signals in MYOD-converted IMR90 fibroblasts. 2b To investigate
MYOD-regulated cis-regulatory elements for satellite cell response to regeneration cues. We will use mouse
models of satellite cell conditional genetic ablation of MyoD or the signal-responsive component of the
SWI/SNF chromatin-remodeling complex BAF60C, to investigate the functional relationship between MYOD,
chromatin remodeling and changes in chromatin interactions for signal-regulated gene expression.
Data from this study will provide fundamental insights into the spatial control of eukaryotic transcription and
satellite cell biology that will favor the transition in regenerative medicine from current therapeutic strategies
affecting glob...

## Key facts

- **NIH application ID:** 9974548
- **Project number:** 5R01GM134712-02
- **Recipient organization:** SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
- **Principal Investigator:** Pier Lorenzo Puri
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $390,000
- **Award type:** 5
- **Project period:** 2019-07-08 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9974548

## Citation

> US National Institutes of Health, RePORTER application 9974548, MYOD Regulation of 3D Chromatin Structure (5R01GM134712-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9974548. Licensed CC0.

---

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