# Function of Protein Methylation in Chromatin and Signaling Regulation

> **NIH NIH R35** · STANFORD UNIVERSITY · 2021 · $627,416

## Abstract

ABSTRACT
Covalent post-translational protein modifications (PTMs) contribute to all aspects of cell physiology and are a
major source of protein functional diversity in mammalian cells. Aberrant regulation of PTMs is a common
feature of human diseases. Our research focuses on two important PTMs: protein methylation at lysine and
histidine residues. Our overarching goal is to elucidate at a molecular level the physiologic roles for lysine and
histidine methylation signaling in the regulation of chromatin biology, epigenetics and other fundamental
biological processes, and to understand how disruption in these mechanisms contributes to human disease.
Within this research framework we will investigate the biology and function of enzymes that regulate histone
methylation dynamics, with a focus on methylation at histone H3 lysine 36 (H3K36). Beyond histone
methylation, there is a growing appreciation that a number of non-histone proteins, including several with clear
roles in gene expression and signal transduction are lysine methylated. Indeed, there are likely far greater than
one hundred lysine methyltransferases in the human genome, and an increasing number of examples of
mutation or translocation of these genes being linked to human disorders. Thus, it is likely that deregulation in
non-histone protein methylation homeostasis plays a crucial role in disease pathogenesis. We will explore the
biology and function of new enzymes and non-histone protein methylation signaling pathways. In addition to
lysine methylation, other residues like histidine are also methylated; though relatively little is known about the
histidine methylation modification network. We will explore the hypothesis that protein histidine methylation has
an underappreciated and significant role in signal transduction, cell biology, and disease pathogenesis. For our
studies, we will use a multi-disciplinary strategy that include biochemical, molecular, proteomic, genomic,
cellular and mouse modeling approaches.

## Key facts

- **NIH application ID:** 10086197
- **Project number:** 1R35GM139569-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Or P. Gozani
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $627,416
- **Award type:** 1
- **Project period:** 2021-03-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10086197

## Citation

> US National Institutes of Health, RePORTER application 10086197, Function of Protein Methylation in Chromatin and Signaling Regulation (1R35GM139569-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10086197. Licensed CC0.

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