# Regulation of non-histone protein function by lysine methylation

> **NIH NIH R35** · INDIANA UNIVERSITY INDIANAPOLIS · 2024 · $389,014

## Abstract

PROJECT SUMMARY:
Reversible lysine methylation is well understood to regulate histone proteins and chromatin templated processes.
Dysregulation of the enzymes responsible for adding (lysine methyltransferases) and removing (lysine
demethylases) lysine methylation is directly associated with many human diseases. In addition to histone
proteins, thousands of non-histone proteins in the human proteome contain lysine methylation, yet we still
understand very little about the function of non-histone lysine methylation. Our long-term goal is to understand
how lysine methylation regulates non-histone protein function and cellular processes. Within this broad
framework, we strive to identify biological processes that are regulated by lysine methylation, the substrate
specificity of KMTs and KDMs, and how dysregulation of lysine methylation signaling contributes to human
disease and developmental disorders. Toward this goal, we recently developed a functional proteomics platform
to profile the substrate selectivity of KMTs and successfully used it to identify the circadian regulator PER2 as a
substrate of lysine methyltransferase SMYD2. We also recently optimized a mass spectrometry pipeline for high-
resolution mapping of lysine methylation. Over the next five years, we will build on this progress and use these
new methods in projects that seek to answer three fundamental questions in the context of the circadian clock
and neuronal differentiation: How big is the lysine methylome? What are the physiologically relevant substrates
for KMTs/KDMs? And what is the function of non-histone lysine methylation? We will answer these questions by
leveraging our strengths in biochemistry, proteomics, genomics, and cell-based studies, to expand our basic
mechanistic understanding of the function of lysine methylation in cellular processes.

## Key facts

- **NIH application ID:** 10914822
- **Project number:** 5R35GM147023-03
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Evan Mitchell Cornett
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $389,014
- **Award type:** 5
- **Project period:** 2022-09-21 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10914822

## Citation

> US National Institutes of Health, RePORTER application 10914822, Regulation of non-histone protein function by lysine methylation (5R35GM147023-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10914822. Licensed CC0.

---

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