# Chromunities Drive Transcriptional Reprogramming in Humoral Immunity and B-cell Lymphomas

> **NIH NIH F31** · WEILL MEDICAL COLL OF CORNELL UNIV · 2024 · $48,974

## Abstract

PROJECT SUMMARY/ABSTRACT
Diffuse large B-cell lymphomas (DLBCL) arise from B-cells transiting different stages of the germinal center
(GC) reaction. It has become clear that these tumors can co-opt regulatory circuits of normal B-cells to drive
their own malignant phenotype. Prior studies observe an inverse correlation between the timing of
transcriptional activation during reprogramming and the degree of topological reorganization near the gene
locus. This suggests that the reorganization of the 3D genome is critical for B-cell development and highlights
its importance in DLBCL. Regulatory hubs are highly interactive regions of enhancers that can form
interactions with multiple genes within topologically associating domains (TADs) to induce gene activation at a
higher probability than pairs of non-interacting genes within the same TAD. Hubs are often rewired during cell
fate transitions. Recent work also suggests a new level of organization into broadly interactive networks called
chromunities, which putatively allow for transboundary sharing of information and more extensive gene
regulatory information critical for cell identity. Critical to understanding the mechanisms driving changes in
gene networks is the study of how large-scale chromosomal rearrangements (structural variants, SVs) can co-
opt regulatory elements to form aberrant or de novo chromunities, consequently driving aberrant gene
expression. While the interpretation of complex structural variants (SVs) has focused primarily on gene
dosage and disruption by aberrant TAD structures, little is known regarding the role of SVs in reprogramming
regulatory hubs and their target genes. To investigate the role of chromunities and its associated hubs in cell
fate transitions and oncogenesis, we will leverage chromatin conformation capture interaction maps (pcHiC,
Pore-C) to develop a computational framework to nominate chromunities and map networks of enhancer and
promoters driving epigenetic and transcriptional reprogramming. We will also integrate chromatin contact maps
with WGS data to investigate the role of complex SVs in reprogramming chromunities in lymphomas. Here, we
hypothesize that physiological reprogramming of chromunity regulatory elements creates de novo coordination
between sets of genes required to establish specific cell states and phenotypes during the humoral immune
response and that SVs occurring in DLBCL alter these hub structures or create new ones leading to selective
advantage of malignant clones. In our first aim, we will integrate transcriptional, epigenetic, and chromatin
conformation capture assays to identify chromunities and their regulatory elements associated with
establishing cell identity in the GC reaction. In our second aim, we will characterize the genomic
rearrangement landscapes of B-cell lymphomas and how these directly link to hubs and chromunities using
patient-derived xenograft models by generating matched WGS, Pore-C, and RNA-seq data.

## Key facts

- **NIH application ID:** 10821323
- **Project number:** 5F31CA271776-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Ceyda Durmaz
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 5
- **Project period:** 2023-09-21 → 2026-09-20

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10821323

## Citation

> US National Institutes of Health, RePORTER application 10821323, Chromunities Drive Transcriptional Reprogramming in Humoral Immunity and B-cell Lymphomas (5F31CA271776-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10821323. Licensed CC0.

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