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Updated: Mar 10, 2026
An Integrated Platform for Genome-wide Mapping of Chromatin States Using High-throughput ChIP-sequencing in Tumor Tissues
Published on: April 5, 2018
Dynamics of BAF-Polycomb complex opposition on heterochromatin in normal and oncogenic states
Cigall Kadoch1,2, Robert T Williams1, Joseph P Calarco3,4
1Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
Abstract:
The opposition between Polycomb repressive complexes (PRCs) and BAF (mSWI/SNF) complexes has a critical role in both development and disease. Mutations in the genes encoding BAF subunits contribute to more than 20% of human malignancies, yet the underlying mechanisms remain unclear, owing largely to a lack of assays to assess BAF function in living cells. To address this, we have developed a widely applicable recruitment assay system through which we find that BAF opposes PRC by rapid, ATP-dependent eviction, leading to the formation of accessible chromatin. The reversal of this process results in reassembly of facultative heterochromatin. Surprisingly, BAF-mediated PRC eviction occurs in the absence of RNA polymerase II (Pol II) occupancy, transcription, and replication. Further, we find that tumor-suppressor and oncogenic mutant BAF complexes have different effects on PRC eviction. The results of these studies define a mechanistic sequence underlying the resolution and formation of facultative heterochromatin, and they demonstrate that BAF opposes PRC on a minute-by-minute basis to provide epigenetic plasticity.
Insights
The BAF (mSWI/SNF) complex opposes Polycomb repressive complexes (PRCs) by rapidly evicting them, creating accessible chromatin. This dynamic epigenetic regulation is crucial for development and preventing cancer.
Area of Science:
- Epigenetics
- Molecular Biology
- Cancer Biology
Background:
- Polycomb repressive complexes (PRCs) and BAF (mSWI/SNF) complexes are key regulators of gene expression.
- Dysregulation of these complexes is implicated in over 20% of human cancers.
- Current assays limit the study of BAF complex function in living cells.
Purpose of the Study:
- To develop a novel assay to assess BAF complex function in living cells.
- To elucidate the mechanism by which BAF complexes oppose PRC activity.
- To investigate the role of BAF complex mutations in cancer.
Main Methods:
- Development of a widely applicable recruitment assay system.
- Assessment of BAF-mediated Polycomb repressive complex eviction.
- Analysis of chromatin accessibility and facultative heterochromatin formation.
- Evaluation of BAF complex behavior in the absence of transcription and replication.
Main Results:
- BAF complexes rapidly and ATP-dependently evict PRCs, leading to accessible chromatin.
- Reversal of this process results in facultative heterochromatin reassembly.
- BAF-mediated eviction occurs independently of RNA polymerase II, transcription, and replication.
- Tumor-suppressor and oncogenic BAF mutants exhibit distinct effects on PRC eviction.
Conclusions:
- BAF complexes dynamically oppose PRCs, providing epigenetic plasticity.
- This mechanism is critical for facultative heterochromatin resolution and formation.
- Understanding this interplay offers insights into cancer development and potential therapeutic strategies.
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