# Hp1bp3 oversees chromatin remodeling to slow tumor growth in high grade glioma

> **NIH NIH F31** · BAYLOR COLLEGE OF MEDICINE · 2024 · $48,974

## Abstract

PROJECT SUMMARY
High grade glioma (HGG) is the most common malignant brain tumor in adults and is universally lethal. The
standard of care for HGG has remained unchanged for over 30 years and median survival is devastatingly low
at only 15 months post diagnosis. Epigenetic aberrations are a key molecular feature that contribute to disease
pathogenesis. Therefore, the goal of this proposal is to define epigenomic dysregulations that promote HGG
growth and determine the mechanisms through which these alterations drive tumorigenesis.
HGG tumors with increased chromatin accessibility tend to have more favorable outcomes. We recently showed
Sox9 inhibits histone deacetylases in HGG to increase H3K27 acetylation, which significantly extends median
survival in mice. Analysis of Sox9 in human HGG revealed it interacts with numerous epigenetic modifying
proteins, including Hp1bp3, a heterochromatin binding protein. Furthermore, whole genome sequencing of
familial glioma patients and their families nominated Hp1bp3 as a potential tumor suppressor, with loss-of-
function (LOF) mutations driving oncogenesis. Using an in-utero electroporation (IUE) mouse model of HGG, we
found that Hp1bp3 loss-of-function (LOF) tumors are hyperproliferative with decreased median survival while
HP1BP3 gain-of-function (GOF) stunts tumor growth and extends survival. Additionally, ATAC-Sequencing of
LOF tumors revealed a global decrease in accessible chromatin. These preliminary results lead me to
hypothesize that Hp1bp3 orchestrates chromatin remodeling to slow tumor growth in HGG.
To understand the role of Hp1bp3 in regulating the epigenome and how this impacts HGG progression, I purpose
three aims. In Aim 1, I will determine the effect of Hp1bp3 in our IUE and PDX models. In the second aim, I will
determine the epigenomic alterations associated with Hp1bp3 by profiling H3Kme3 and H4K20me3 marks which
appear to be altered by Hp1bp3 in HGG. Lastly, ChIP-Seq on Hp1bp3 in HGG mouse tumor revealed Hp1bp3
binds DNA at gene loci involved with methionine and one-carbon metabolism. Therefore, aim three will identify
the metabolic changes in Hp1bp3 mutant tumors using metabolomics and determine how these alterations drive
tumor growth.
Overall, this research aims to expand our understanding of how epigenetic dysregulation in HGG drives disease
progression. Importantly, this work will nominate new epigenetic candidates as potential drug targets in HGG.

## Key facts

- **NIH application ID:** 10997119
- **Project number:** 1F31CA295034-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Brittney Lozzi
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 1
- **Project period:** 2024-07-09 → 2026-07-08

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10997119

## Citation

> US National Institutes of Health, RePORTER application 10997119, Hp1bp3 oversees chromatin remodeling to slow tumor growth in high grade glioma (1F31CA295034-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10997119. Licensed CC0.

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