# Elucidating the role of REST in shaping the epigenome of melanoma

> **NIH NIH F30** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $44,436

## Abstract

PROJECT SUMMARY
Melanoma is the most aggressive form of skin cancer with rising incidence. Despite significant advances,
available therapies are effective only in distinct subsets of patients where relapse, treatment-refractory disease,
and/or significant toxicities commonly occur. It has become increasingly evident that epigenetic alterations that
lead to aberrant gene expression programs play an integral role in melanoma initiation and development.
Repressor Element-1 (RE-1) Silencing Transcription (REST), a zinc finger transcription factor (TF), has been
implicated in a diverse subset of cancers as pro-proliferative in neural tumors and anti-proliferative in non-neural
tumors. REST binds DNA in a sequence-specific manner at RE1 motifs and primarily functions to repress
neuronal gene transcription in non-neuronal cells. REST-mediated gene repression is achieved by the
recruitment of several chromatin modifying complexes to DNA that erase active histone marks and write
repressive marks. Relevant to my proposal, TCGA data indicates that REST is overexpressed in metastatic
melanoma compared to primary melanoma. Yet to date, there are no studies that have explored REST in
regulating aberrant gene expression programs in melanoma. I found that REST loss-of-function impairs
melanoma proliferation by inducing cell cycle arrest and subsequent apoptosis. RNA-sequencing analysis upon
REST knockdown revealed that REST regulates key melanoma survival genes, enriched in pathways related to
Cadherin, p38, and Wnt Signaling. Together, my phenotypic and transcriptomic analysis of REST depletion
demonstrated, for the first time, that melanoma cells are dependent on REST. In this proposal, I seek to continue
to test my hypothesis that through the modulation of the epigenetic landscape, REST regulates pro-tumorigenic
transcriptional programs in melanoma, utilizing a combination of functional and genomic approaches. I expect
my findings to open avenues for investigation into the molecular mechanisms and cellular functions of REST and
ultimately, to present a novel therapeutic strategy for melanoma patients.

## Key facts

- **NIH application ID:** 10198753
- **Project number:** 5F30CA253988-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Christie Bao Thu Nguyen
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $44,436
- **Award type:** 5
- **Project period:** 2020-06-18 → 2024-06-17

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10198753

## Citation

> US National Institutes of Health, RePORTER application 10198753, Elucidating the role of REST in shaping the epigenome of melanoma (5F30CA253988-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10198753. Licensed CC0.

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