Cell Reports (Apr 2022)
Altered BAF occupancy and transcription factor dynamics in PBAF-deficient melanoma
- Saul Carcamo,
- Christie B. Nguyen,
- Elena Grossi,
- Dan Filipescu,
- Aktan Alpsoy,
- Alisha Dhiman,
- Dan Sun,
- Sonali Narang,
- Jochen Imig,
- Tiphaine C. Martin,
- Ramon Parsons,
- Iannis Aifantis,
- Aristotelis Tsirigos,
- Julio A. Aguirre-Ghiso,
- Emily C. Dykhuizen,
- Dan Hasson,
- Emily Bernstein
Affiliations
- Saul Carcamo
- Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute Bioinformatics for Next Generation Sequencing (BiNGS) Shared Resource Facility, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- Christie B. Nguyen
- Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- Elena Grossi
- Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- Dan Filipescu
- Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- Aktan Alpsoy
- Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA
- Alisha Dhiman
- Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA
- Dan Sun
- Division of Hematology and Oncology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- Sonali Narang
- Department of Pathology and Laura & Isaac Perlmutter Cancer Center, New York, NY 10016, USA
- Jochen Imig
- Department of Pathology and Laura & Isaac Perlmutter Cancer Center, New York, NY 10016, USA
- Tiphaine C. Martin
- Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- Ramon Parsons
- Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- Iannis Aifantis
- Department of Pathology and Laura & Isaac Perlmutter Cancer Center, New York, NY 10016, USA
- Aristotelis Tsirigos
- Department of Pathology and Laura & Isaac Perlmutter Cancer Center, New York, NY 10016, USA; Applied Bioinformatics Laboratories, NYU School of Medicine, New York, NY 10016, USA
- Julio A. Aguirre-Ghiso
- Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Division of Hematology and Oncology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Otolaryngology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- Emily C. Dykhuizen
- Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA
- Dan Hasson
- Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute Bioinformatics for Next Generation Sequencing (BiNGS) Shared Resource Facility, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- Emily Bernstein
- Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Corresponding author
- Journal volume & issue
-
Vol. 39,
no. 1
p. 110637
Abstract
Summary: ARID2 is the most recurrently mutated SWI/SNF complex member in melanoma; however, its tumor-suppressive mechanisms in the context of the chromatin landscape remain to be elucidated. Here, we model ARID2 deficiency in melanoma cells, which results in defective PBAF complex assembly with a concomitant genomic redistribution of the BAF complex. Upon ARID2 depletion, a subset of PBAF and shared BAF-PBAF-occupied regions displays diminished chromatin accessibility and associated gene expression, while BAF-occupied enhancers gain chromatin accessibility and expression of genes linked to the process of invasion. As a function of altered accessibility, the genomic occupancy of melanoma-relevant transcription factors is affected and significantly correlates with the observed transcriptional changes. We further demonstrate that ARID2-deficient cells acquire the ability to colonize distal organs in multiple animal models. Taken together, our results reveal a role for ARID2 in mediating BAF and PBAF subcomplex chromatin dynamics with consequences for melanoma metastasis.
