# Regulation of gene expression by chromatin remodeling enzymes

> **NIH NIH R35** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2022 · $420,427

## Abstract

PROJECT SUMMARY
To understand normal development and differentiation, it is necessary to determine the mechanisms by which
cells initiate new programs of gene expression and promote the formation of specific cell lineages. Typically,
this involves activation of genes that are transcriptionally silent and that are likely incorporated into repressive
chromatin structure. Evidence supports the idea that differentiation-specific transcriptional regulators and
enzymes that remodel or alter chromatin structure cooperate to render genomic DNA more accessible to the
transcriptional machinery. The mammalian SWI/SNF (mSWI/SNF) enzyme family members remodel
nucleosome structure in an ATP dependent manner and facilitate transcription factor function in vitro and in
vivo. Components of these enzymes are essential for embryonic development and some can act as tumor
suppressors or tumor promoters. Additionally, SWI/SNF enzymes are implicated in cell cycle control. Thus
these enzymes are broadly required for normal cell function and for differentiation and development, and their
misregulation is implicated in tumor formation.
Skeletal muscle differentiation has long been a model for studying fundamental principles of tissue-specific
gene expression and differentiation. The SWI/SNF chromatin remodeling enzymes play essential roles in
these processes. This project will focus on the mechanisms by which different kinases and phosphatases
involved in signaling pathways regulate the phosphorylation and function of SWI/SNF chromatin remodeling
enzyme subunits in proliferating and differentiating myoblasts. We will employ methods to manipulate the
expression of specific kinases, phosphatases and remodeling enzyme subunits and will manipulate function
through use of inhibitors and mutagenensis. We will analyaze the effects of such approaches on gene
expression, chromatin binding and remodeling, transcription factor function, local higher-order gene structure,
and overall genome organization. The work will provide new paradigms for understanding how signaling
molecules converge on chromatin to regulate tissue differentiation and development.

## Key facts

- **NIH application ID:** 10376358
- **Project number:** 5R35GM136393-03
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** ANTHONY N IMBALZANO
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $420,427
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10376358

## Citation

> US National Institutes of Health, RePORTER application 10376358, Regulation of gene expression by chromatin remodeling enzymes (5R35GM136393-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10376358. Licensed CC0.

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