# Deciphering the Role of ACTL6a in Central Nervous System Myelination

> **NIH NIH F31** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $43,920

## Abstract

Project Summary
Oligodendrocytes are the myelinating cells of the central nervous system, making their function critical for axonal
survival and proper conduction of action potentials. Oligodendrocytes are derived from oligodendrocyte
progenitors (OPCs) and their differentiation is orchestrated by a balance of epigenetic repression by histone and
DNA modifying enzymes and transcriptional activation by chromatin remodelers. These epigenetic events have
been shown to be modulated by both chemical and mechanical external stimuli. While the repressive events
driving oligodendrocyte differentiation have been well-studied, significantly less is known about the
transcriptional activation by chromatin remodelers and how their activity is modulated by extrinsic signals. Prior
studies have shown that compressive force induces both enhanced myelination and a rapid influx of monomeric
actin into the OPC nucleus. Monomeric actin has been shown to bind strongly to an actin-related protein called
ACTL6a, which is a component of the SWI/SNF chromatin remodeling complex, whose function is critical for
oligodendrocyte differentiation. My proposal thus utilizes both in vitro and in vivo models to investigate the
mechanism through which ACTL6a modulates the epigenetic events that regulate oligodendrocyte
differentiation.
Using characterizations of mice with Actl6a ablated at various stages of the oligodendrocyte lineage, I found that
ACTL6a is critical for early OPC differentiation. My preliminary data additionally revealed an increase in ACTL6a
in response to both chemical and mechanical inducers of differentiation. Biochemical investigation further
revealed that ACTL6a interacts with several components of the transcriptional machinery and the SWI/SNF
chromatin remodeling complex. Based on these results, my proposal tests the hypothesis that ACTL6a
modulates OPC differentiation through the recruitment of chromatin remodelers and the transcriptional
machinery to activate gene expression. The results of this proposal will ultimately shed light on a critical
mechanism through which ACTL6a, an actin-related protein, modulates chromatin remodeling and the epigenetic
landscape of OPCs during differentiation and developmental myelination.

## Key facts

- **NIH application ID:** 9991643
- **Project number:** 5F31NS110166-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Eric Tsai
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $43,920
- **Award type:** 5
- **Project period:** 2019-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991643

## Citation

> US National Institutes of Health, RePORTER application 9991643, Deciphering the Role of ACTL6a in Central Nervous System Myelination (5F31NS110166-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9991643. Licensed CC0.

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