# Gene-specific transcriptional silencing by REST function

> **NIH NIH R01** · UNIVERSITY OF TEXAS AT AUSTIN · 2022 · $318,933

## Abstract

PROJECT SUMMARY
 The RE-1 silencing transcription factor (REST), also known as Neuron-Restrictive Silencer Factor
(NRSF), is a master regulator that represses the expression of neuronal genes in stem cell and non-neuronal cells.
Overexpression of REST leads to the development of several types of brain tumors, and its dysregulation has
been detected in multiple neurological diseases. The huge discrepancy arises reporting different genes subject to
REST control, which might be due to the dose- and cell type-dependency of REST in different contexts. In this
grant, we will test the hypothesis that REST transcriptional silencing activity can be controlled by small molecule
inhibitors of the regulatory protein of REST we have developed. Particularly, we will investigate the cytotoxic
effect of these inhibitors in glioblastoma cells when REST drives tumor growth. Furthermore, we will understand
at the atomic level the molecular mechanism of REST function through quantitative assessment of its interaction
with its DNA targets and its co-repressors for gene silencing. In the long run, we want to identify small molecule
inhibitors to treat diseases driven by excess REST activity.

## Key facts

- **NIH application ID:** 10401469
- **Project number:** 5R01GM104896-08
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Yan Jessie Zhang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $318,933
- **Award type:** 5
- **Project period:** 2013-08-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10401469

## Citation

> US National Institutes of Health, RePORTER application 10401469, Gene-specific transcriptional silencing by REST function (5R01GM104896-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10401469. Licensed CC0.

---

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