# Role of DNA Methylation in Liquid-liquid Phase Separation-mediated Heterochromatin Formation

> **NIH NIH R35** · UPSTATE MEDICAL UNIVERSITY · 2021 · $80,269

## Abstract

Project Summary/Abstract
The structure and dynamics of chromatin control the accessibility of DNA to regulatory factors during
transcription, replication, recombination and DNA damage repair. PTMs of chromatin-associated proteins and
DNA methylation are complex epigenetic mechanisms that regulate gene expression and chromatin
organization. The interplay between these mechanisms generate synergistic or antagonistic interactions that
partition chromatin into (i) euchromatin: lightly packed chromatin, enriched in genes often under active
transcription or (ii) heterochromatin: tightly packed and condensed chromatin, containing mostly silenced genes.
The molecular mechanisms underlying this partition is not fully understood. Recent studies demonstrate that
heterochromatin can assemble through liquid-liquid phase separation (LLPS) driven by multivalent interactions
between modified histone tails and the proteins that bind these epigenetic modifications. However,
heterochromatin is also highly enriched in methylated DNA, which is reciprocally regulating, and regulated by
the surrounding histone modification binding proteins and enzymes. How methylated DNA binding proteins and
the patterns of DNA methylation co-ordinate with the histone modification machinery in the LLPS-mediated
assembly of heterochromatin is not fully understood. This proposal will address these gaps in knowledge.

## Key facts

- **NIH application ID:** 10389052
- **Project number:** 3R35GM138097-02S1
- **Recipient organization:** UPSTATE MEDICAL UNIVERSITY
- **Principal Investigator:** Alaji Bah
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $80,269
- **Award type:** 3
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10389052

## Citation

> US National Institutes of Health, RePORTER application 10389052, Role of DNA Methylation in Liquid-liquid Phase Separation-mediated Heterochromatin Formation (3R35GM138097-02S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10389052. Licensed CC0.

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