# Structure-activity relationships governing mammalian SWI/SNF chromatin remodeling activity as a function of chromatin state

> **NIH NIH R01** · DANA-FARBER CANCER INST · 2021 · $709,868

## Abstract

PROJECT SUMMARY
Recent whole-exome sequencing studies in human cancer and neurodevelopmental disorders have unmasked
frequent mutations in genes encoding chromatin regulatory proteins. Specifically, genes encoding subunits of
the mammalian SWI/SNF ATP-dependent chromatin remodeling complexes (also called mSWI/SNF or BAF
complexes) are perturbed in over 20% of malignancies, underscoring their critical roles in the maintenance of
timely and appropriate gene expression. The mechanisms by which mSWI/SNF family complexes are targeted
on chromatin and the features of the histone landscape that govern their activities remain unknown. Indeed, a
systematic evaluation defining the contributions of specific histone landscape features to canonical BAF, PBAF,
and non-canonical BAF complex targeting and activity would represent a significant advancement in the field at-
large. Here we aim to: (1) Determine the genome-wide targeting of distinct, final-form mSWI/SNF complexes in
human cells and the impact of select cancer-associated complex perturbations; (2) Define the in vitro
nucleosome remodeling and ATPase activities of endogenously-purified mSWI/SNF subcomplexes, BAF, PBAF,
and ncBAF, in wild-type (WT) and mutant states; and (3) Determine the impact of core histone variants and
histone tail modifications on mSWI/SNF complex nucleosome binding and activity. Taken together, successful
completion of these aims centered at the intersection of biochemistry, epigenetics, and cancer biology, will
constitute a highly timely series of advances in the field of chromatin biology, and will contribute important
knowledge regarding the mechanism of targeting of mSWI/SNF complexes across a range of both normal and
oncogenic states. Given that a major impediment to the development of on-target modulatory agents of
mSWI/SNF complexes lies in the lack of biological understanding of complex-specific targeting and functional
regulation, the results of this proposal are likely to provide the basis for new approaches toward targeted
disruption of mSWI/SNF-chromatin interactions.

## Key facts

- **NIH application ID:** 10184885
- **Project number:** 1R01CA259365-01
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** Cigall Kadoch
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $709,868
- **Award type:** 1
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10184885

## Citation

> US National Institutes of Health, RePORTER application 10184885, Structure-activity relationships governing mammalian SWI/SNF chromatin remodeling activity as a function of chromatin state (1R01CA259365-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10184885. Licensed CC0.

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