# How MeCP2 discriminates epigenetic marks is still a mystery

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2020 · $334,000

## Abstract

Abstract
The X chromosome coded `Methyl CpG binding protein 2' (MECP2) is highly expressed in neuronal
tissues and named for its recognition of the methyl-CpG (mCpG) epigenetic modification. The
importance of MeCP2 to neuronal and brain development is highlighted by the fact that MeCP2
mutations cause >90% of the diagnosed cases of the autism spectrum disorder Rett syndrome.
Recent genomic studies have raised important questions regarding the full range of DNA sequences
and types of base modifications bound by the protein. Our proposed studies seek to determine the
molecular mechanisms underlying specific recognition of the type of nucleotide modification, DNA
sequence, and binding cooperativity that meld to mediate localization of MeCP2 on chromatin. Our
project interleaves energetic and structural analyses proposing quantitative assembly studies to
determine the combinations of nucleotide modification with local and flanking DNA sequences that
confer high specificity MeCP2 binding, the structure of MeCP2 - DNA complexes to reveal if
differences exist among the bound target sites, and determine how MeCP2 competes with linker
histones on chromatin and subsequently localizes to specific sites. Our proposal integrates
established and novel quantitative and structural approaches to explore how binding of this key
regulatory protein to chromatin initiates a cascade of molecular interactions that guides neuronal
development.

## Key facts

- **NIH application ID:** 9951072
- **Project number:** 5R01GM129350-04
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Michael D. Brenowitz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $334,000
- **Award type:** 5
- **Project period:** 2018-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9951072

## Citation

> US National Institutes of Health, RePORTER application 9951072, How MeCP2 discriminates epigenetic marks is still a mystery (5R01GM129350-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9951072. Licensed CC0.

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