# Defining the role of the BCL7 subunit of mammalian SWI/SNF chromatin remodeling complexes in human cancer

> **NIH NIH F31** · HARVARD MEDICAL SCHOOL · 2022 · $40,496

## Abstract

PROJECT SUMMARY/ABSTRACT
The mammalian SWI/SNF (mSWI/SNF) complexes represent a family of ATP-dependent chromatin remodeling
complexes (CRCs) that play critical roles in the maintenance of chromatin accessibility and gene expression.
Mammalian SWI/SNF complexes are combinatorically assembled from 29 different gene products to generate
three distinct 11-15-subunit classes termed BAF, pBAF, and ncBAF complexes. Importantly, mSWI/SNF genes
are mutated in over 20% of human cancers, underscoring their critical roles in oncogenesis. While biochemical,
structural and genomics-based studies over the past several years have begun to define subunit-specific
contributions to overall protein complex function, most subunit functions remain unassigned. BCL7 is a recently-
discovered component of all three SWI/SNF complex classes. Despite other mSWI/SNF complex subunits being
conserved throughout evolution, BCL7 has only recently emerged in higher-order organisms, suggesting it may
be necessary for specialized organismal processes such as mammalian cell differentiation or immune system
development. I aim to define the role of the BCL7 subunit in mSWI/SNF complex function in the human cell
context.
I hypothesize that BCL7 is required for a) SWI/SNF complex biochemical integrity; and b) for genome-wide
SWI/SNF targeting and DNA accessibility generation in lymphoma and primary B cells. The role of the
mammalian-specific BCL7 subunit in the biochemical composition, targeting, and activity of SWI/SNF complexes
remains unknown. First, I aim to determine the impact of BCL7 deletion on SWI/SNF complex biochemical
integrity (subunit assembly and stability) and to define the region of BCL7 required for its incorporation into
SWI/SNF complexes. BCL7 mutations, including deletions and single-residue substitutions, have been identified
primarily in lymphomas and myelomas, cancer subtypes that affect B cell maturation and function. Second, I aim
to determine the impact of BCL7 perturbations on the SWI/SNF complex genomic targeting, DNA accessibility
generation, and subsequent gene expression in B cell lymphomas such as DLBCL. Third, I aim to determine the
functional impact and role of BCL7 in SWI/SNF complex genomic targeting and accessibility generation in
healthy human primary B cells.
This research will elucidate key features of BCL7-mediated SWI/SNF complex composition, chromatin
localization, and resulting DNA accessibility, and gene expression programs in normal and malignant B cells.
The mechanisms governing chromatin remodeling complex activities during basic cellular processes and in
human disease remain incompletely understood, and with the highly frequent mutations in these processes
observed in human cancers, this is a uniquely pertinent and high-impact priority for the field at-large.

## Key facts

- **NIH application ID:** 10450322
- **Project number:** 1F31CA271427-01
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Kimberlee Hixon
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $40,496
- **Award type:** 1
- **Project period:** 2022-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10450322

## Citation

> US National Institutes of Health, RePORTER application 10450322, Defining the role of the BCL7 subunit of mammalian SWI/SNF chromatin remodeling complexes in human cancer (1F31CA271427-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10450322. Licensed CC0.

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