# MeCP2 and non-CG methylation regulation of neuronal cell-type specific transcription

> **NIH NIH F30** · WASHINGTON UNIVERSITY · 2022 · $51,752

## Abstract

Project Summary: Mutations in transcriptional regulatory proteins have been identified as a major cause of
neurodevelopmental disorders such as autism and intellectual disability. To understand how these proteins drive
disease pathology, we need to first develop a mechanistic understanding of how these regulators contribute to
normal neurodevelopment. Alterations in methyl-CpG binding protein 2 (MeCP2) results in Rett Syndrome
(RTT), a severe neurodevelopmental disorder, and MeCP2 Duplication Syndrome, an autism spectrum
disorder. MeCP2 has been shown to bind both methylated CG dinucleotides and a neuron-enriched form of
methylation at cytosines in non-CpG contexts (mCA). Loss of MeCP2 leads to increased expression of long
neuronal genes (>100kb) that are enriched for mCA within their gene body. Interestingly, mCA and MeCP2
have been shown to regulate gene expression in a cell-type specific manner. The long-term goal of our lab is
to understand the function of MeCP2 and mCA transcriptional regulation in the nervous system and how their
dysfunction results in neurological disorders.
 This proposal will determine how MeCP2 and mCA control cell-type specific gene expression programs
through control of regulatory elements and in cooperation with genome topology. In Aim 1, I will test the
hypothesis that MeCP2 regulates cell-type specific enhancers to drive gene expression programs in individual
neurons. In Aim 2, I will further understand this regulatory mechanism by analyzing how chromatin architecture
drives cell-type specific mCA patterns. The results from these experiments will provide important insights into
the mechanism and function of MeCP2 and mCA and how they produce pathology when disrupted.

## Key facts

- **NIH application ID:** 10474264
- **Project number:** 5F30HD102147-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** James Russell Moore
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $51,752
- **Award type:** 5
- **Project period:** 2021-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10474264

## Citation

> US National Institutes of Health, RePORTER application 10474264, MeCP2 and non-CG methylation regulation of neuronal cell-type specific transcription (5F30HD102147-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10474264. Licensed CC0.

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