# Mechanistic Insights into Mammalian DNA Methylation

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA RIVERSIDE · 2020 · $117,022

## Abstract

Mechanistic Insights into Mammalian DNA Methylation
ABSTRACT
 DNA methylation is a major epigenetic mechanism that is essential for transcriptional
silencing of retrotransposons, genomic imprinting and X-chromosome inactivation. Aberrant
DNA methylation patterns lead to genomic and chromosomal instability and silencing of tumor
suppressor genes, which contribute to the development of cancer and many other human
diseases. DNA methylation patterns in mammalian genomes are dynamically established and
maintained by two groups of DNA methyltransferases (DNMTs): DNMT3A and DNMT3B, which
together establish DNA methylation patterns during gametogenesis and early embryogenesis,
and DNMT1, which propagates DNA methylation patterns in differentiated cells. The molecular
mechanisms of both groups of DNMTs remain a long-standing and fundamental question. The
long-term goals of the PI's research are: (a) to provide a comprehensive understanding of how
the DNA methylation machinery is regulated, and (b) to determine the relationship between the
regulation of DNA methylation and human diseases. The biochemical and cellular functions of
DNMTs are subject to both intramolecular and intermolecular regulations. How these
regulations cooperate in controlling mammalian DNA methylation has not been well
characterized. Our research program will focus on addressing these important challenges of
mammalian DNA methylation through an approach that integrates structural biology with
biochemistry, molecular biology and cell biology. The objective of this application is to provide a
deep mechanistic understanding of DNMT1-mediated maintenance DNA methylation and
DNMT3A-mediated de novo DNA methylation. We will provide structural basis for the
conformational dynamics of DNMT1 and its regulatory protein UHRF1, the interaction between
DNMT1 and UHRF1, and the substrate recognition of DNMT3A. Guided by these structural
studies, we will further investigate how the regulations of DNMTs influence genomic DNA
methylation. Together, these studies will bring our mechanistic understanding of mammalian
DNA methylation to the next level.

## Key facts

- **NIH application ID:** 10135433
- **Project number:** 3R35GM119721-05S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA RIVERSIDE
- **Principal Investigator:** Jikui Song
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $117,022
- **Award type:** 3
- **Project period:** 2016-08-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135433

## Citation

> US National Institutes of Health, RePORTER application 10135433, Mechanistic Insights into Mammalian DNA Methylation (3R35GM119721-05S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10135433. Licensed CC0.

---

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