# Dissecting functional roles of MeCP2 condensates in neurons with chemogenetic tools

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $242,250

## Abstract

Project Summary
Nuclear condensate formation by chromatin regulatory proteins and transcription factors is a new paradigm for
explaining genome partitioning and gene regulation mechanisms. Recent studies showed that disease-
associated mutations of DNA-binding protein, such as MeCP2, are associated with aberrant condensate
formation and disrupting the heterochromatin domains. However, the most current studies of phase-separation
by nuclear proteins are limited to in vitro biochemical studies and overexpression studies in cells showing the
formation of puncta or nuclear bodies, which are insufficient to dissect the molecular function of endogenous
protein condensates in disease. To address these issues, the objective of this R21 application is to develop
novel chemogenetic tools for manipulating, monitoring, and testing endogenous MeCP2 condensates in neurons.
Specifically, we will develop SPARK-OFF to dissolve MeCP2 condensates and SPARK-ON to restore
condensation for MeCP2 mutants from Rett Syndrome patients in differentiated neurons. Through sequencing
analysis, we will further investigate the roles of MeCP2 condensates in chromatin regulation, chromatin structure,
and gene regulation. Our study will provide new technologies for studying the biological function of nuclear
condensates in the nervous system and help demystify the causal relationship between MeCP2 condensates
and Rett Syndrome etiology.

## Key facts

- **NIH application ID:** 10487879
- **Project number:** 1R21DA056293-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Yin Shen
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $242,250
- **Award type:** 1
- **Project period:** 2022-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10487879

## Citation

> US National Institutes of Health, RePORTER application 10487879, Dissecting functional roles of MeCP2 condensates in neurons with chemogenetic tools (1R21DA056293-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10487879. Licensed CC0.

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