# Gene-specific responses to NF-kB through lysine and arginine methylation of p65

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2020 · $10,952

## Abstract

NIGMS RO1, PI: Tao Lu, Ph.D.
Title: Gene-specific responses to NF-κB through lysine and arginine methylation of p65
Abstract:
Activation of the multi-functional transcription factor nuclear factor κB (NF-κB), a central coordinator of immune
responses, is tightly regulated in order to achieve its normal transient activation in response to stress. In many
pathologies, NF-κB is activated abnormally, contributing to the development of a variety of disorders, including
lung disease, chronic inflammatory diseases, cardiovascular disease, diabetes, and cancer. Thus, drugs that
block NF-κB activation could be effective in treating these diseases. Understanding the molecular mechanism
of NF-κB activation is the first step toward our long-term goal of identifying novel therapeutics. This proposal
focuses on methylation as a novel mechanism ensuring precise control of NF-κB activity at its target genes.
Recently, we discovered that lysine residues 218/221 (K218/221) and arginine residue 30 (R30) of the p65
subunit of NF-κB are methylated by histone-modifying enzymes. Our central hypothesis is that p65 R30 and
K218/221 methylation differentially regulates NF-κB-dependent gene expression by affecting promoter binding,
recruitment of transcriptional modifiers, and the physical properties of the NF-κB:DNA interaction. To test this
central hypothesis, we will pursue two specific aims: Aim 1: Dissect the distinct impacts of p65 R30 and K218/221
methylation on the critical molecular events that lead to differential gene regulation. Aim 2: Determine the
structural consequences of p65 R30 methylation, and discover the mechanisms of NF-κB-DNA sequence-
specific effects on target gene promoters. Significance: The important findings from this study will identify the
molecular mechanisms underlying p65 methylation-dependent gene-specific regulation, thus revealing how the
extreme plasticity of biological responses is regulated by NF-κB, and offering deep insights into the development
of NF-κB-associated diseases as well as innovative strategies for their therapeutic intervention.

## Key facts

- **NIH application ID:** 10145947
- **Project number:** 3R01GM120156-03S1
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Tao Lu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $10,952
- **Award type:** 3
- **Project period:** 2017-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10145947

## Citation

> US National Institutes of Health, RePORTER application 10145947, Gene-specific responses to NF-kB through lysine and arginine methylation of p65 (3R01GM120156-03S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10145947. Licensed CC0.

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