# Epstein-Barr Virus nuclear antigen leader protein in transcription regulation

> **NIH NIH K99** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $86,916

## Abstract

Abstract:
Epstein-Barr virus (EBV) associated diseases remain a huge burden in human health. As an
orally transmitted pathogen, EBV infection causes infectious mononucleosis and ~200,000
cases of various cancers, including nasopharyngeal carcinoma that occurs in a space
immediately adjacent to the oral cavity, some B cell malignancies, and ~10% of gastric cancer.
In HIV infected people, EBV causes oral hairy leukoplakia of tongue. To understand the
molecular mechanisms through which EBV contributes to disease development,
EBV-transformed lymphoblastoid cell lines are used as a model system. EBV nuclear antigen
leader protein (EBNALP) is essential for EBV to transform naïve B lymphocytes. Most of its
known functions are linked to EBV transcription activator EBNA2. However, EBNALP binds to
many enhancer and promoter sites independent of EBNA2. Perturbations of these EBNALP
sites with CRISPRi significantly decreased these enhancers’ linked gene expression. Little is
known about how EBNALP exerts its EBNA2 independent functions. It is also not known how
EBNALP is tethered to the enhancer/promoter sites and how they affect transcription.
Therefore, we hypothesize that EBNALP exploits host transcription programs to gain
access to host enhancers/promoters, and contributes to EBV transformation through
EBNA2-independent mechanisms. During my mentored period, I will address the
fundamental question of how EBNALP binds to DNA. We will use CRISPR-based assays to
identify host proteins essential for EBNALP enhancer activation. I will first focus on
sequence-specific transcription factors (TFs). Chromatin immune precipitation (ChIP) based
assays will be used to test the effects of knockout on EBNALP DNA binding. During my R00
phase, I will perform research independently and distinguish my work from my mentor’s by
studying different aspects of EBNALP. I will focus my studies on characterizing the enhancer
protein complexes assembled by EBNALP onto the enhancers to regulate transcription
activity. I will focus on transcription cofactors, basal transcription factors, and histone
modifying enzymes. Understanding the mechanisms through which EBNALP binds to DNA
and regulates gene transcription may provide promising targets for treating EBV-associated
diseases.

## Key facts

- **NIH application ID:** 10331840
- **Project number:** 5K99DE030215-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Chong Wang
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $86,916
- **Award type:** 5
- **Project period:** 2021-02-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10331840

## Citation

> US National Institutes of Health, RePORTER application 10331840, Epstein-Barr Virus nuclear antigen leader protein in transcription regulation (5K99DE030215-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10331840. Licensed CC0.

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