@article{619fc6ad40b648f79bee57588a1536df,
title = "Altered BAF occupancy and transcription factor dynamics in PBAF-deficient melanoma",
abstract = "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.",
keywords = "ARID2, BAF, CP: Cancer, PBAF, SWI/SNF, chromatin, invasion, melanoma, transcription factors",
author = "Saul Carcamo and Nguyen, {Christie B.} and Elena Grossi and Dan Filipescu and Aktan Alpsoy and Alisha Dhiman and Dan Sun and Sonali Narang and Jochen Imig and Martin, {Tiphaine C.} and Ramon Parsons and Iannis Aifantis and Aristotelis Tsirigos and Aguirre-Ghiso, {Julio A.} and Dykhuizen, {Emily C.} and Dan Hasson and Emily Bernstein",
note = "Funding Information: The authors thank the laboratories of David Fisher, Brian Brown, Javier Bravo-Cordero, Eva Hernando, Robert Kerbel, and Poulikos Poulikakos for reagents and advice; Ana Hahn, Kent Madrid, and Kevin Mohammed for NGS support; Daniel Munguia for experimental assistance; the Bernstein lab for discussions and feedback; Jill Gregory for illustrations; NYU Genome Technology Center (GTC), and both the Applied Bioinformatics Laboratories (ABL) at NYU and the Bioinformatics for Next Generation Sequencing (BiNGS) core at the Icahn School of Medicine at Mount Sinai (ISMMS) for bioinformatic support. This study was supported by NIH/NCI F30 CA253988-02 to C.B.N.; Philippe Foundation to T.C.M.; American-Italian Cancer Foundation and National Cancer Center to E.G.; American Skin Association to D.F.; NIH/NCI P01CA229086, R01CA242020, and R01CA228135 to I.A.; NIH/NCI P01CA229086 and NIH/NCI R01CA252239 to A.T.; NIH/NCI U01CA207532 to E.C.D.; NCI P30 CA196521 to R.P.; NIH/NCI CA109182, CA216248, CA218024, and CA196521 to J.A.A.-G.; and NIH/NCI R01CA154683 and CA218024 to E.B. J.A.A.-G. is a Samuel Waxman Cancer Research Foundation Investigator. This work was supported in part through the Oncological Sciences Sequencing Core supported by Tisch Cancer Institute of the ISMMS Cancer Center, support grant P30CA196521; Scientific Computing supported by the Office of Research Infrastructure of the NIH under award no. S10OD026880 to ISMMS; and the ISMMS Genomics Technology Facility, NYU GTC and ABL and shared resources partially supported by the Cancer Center support grant P30CA016087 at the Laura and Isaac Perlmutter Cancer Center. This work utilized computing resources at the NYU High Performance Computing Facility. Conceptualization, S.C. D.H. and E.B.; investigation, S.C. D.H. C.B.N. E.G. D.F. A.A. A.D. J.I. and D.S.; formal analysis, S.C. D.H. C.B.N. and T.C.M.; writing – original draft, S.C. and E.B; writing – review & editing, S.C. D.H. C.B.N. E.G. D.F. J.A.A.-G. T.C.M. E.C.D. and E.B.; visualization, S.C. and D.H.; resources, expertise, and methods, I.A. J.A.A.-G. R.P. A.T. and E.C.D.; data curation, S.C. C.B.N. S.N. and D.H.; supervision, E.C.D. D.H. and E.B.; funding acquisition, R.P. J.A.A.-G. E.C.D. and E.B. J.A.A.-G. is a scientific co-founder, scientific advisory board member, and equity owner of HiberCell and receives financial compensation as a consultant. Funding Information: The authors thank the laboratories of David Fisher, Brian Brown, Javier Bravo-Cordero, Eva Hernando, Robert Kerbel, and Poulikos Poulikakos for reagents and advice; Ana Hahn, Kent Madrid, and Kevin Mohammed for NGS support; Daniel Munguia for experimental assistance; the Bernstein lab for discussions and feedback; Jill Gregory for illustrations; NYU Genome Technology Center (GTC), and both the Applied Bioinformatics Laboratories (ABL) at NYU and the Bioinformatics for Next Generation Sequencing (BiNGS) core at the Icahn School of Medicine at Mount Sinai (ISMMS) for bioinformatic support. This study was supported by NIH / NCI F30 CA253988-02 to C.B.N.; Philippe Foundation to T.C.M.; American-Italian Cancer Foundation and National Cancer Center to E.G.; American Skin Association to D.F.; NIH / NCI P01CA229086 , R01CA242020 , and R01CA228135 to I.A.; NIH / NCI P01CA229086 and NIH / NCI R01CA252239 to A.T.; NIH / NCI U01CA207532 to E.C.D.; NCI P30 CA196521 to R.P.; NIH / NCI CA109182 , CA216248 , CA218024 , and CA196521 to J.A.A.-G.; and NIH / NCI R01CA154683 and CA218024 to E.B. J.A.A.-G. is a Samuel Waxman Cancer Research Foundation Investigator. This work was supported in part through the Oncological Sciences Sequencing Core supported by Tisch Cancer Institute of the ISMMS Cancer Center, support grant P30CA196521 ; Scientific Computing supported by the Office of Research Infrastructure of the NIH under award no. S10OD026880 to ISMMS; and the ISMMS Genomics Technology Facility, NYU GTC and ABL and shared resources partially supported by the Cancer Center support grant P30CA016087 at the Laura and Isaac Perlmutter Cancer Center. This work utilized computing resources at the NYU High Performance Computing Facility. Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = apr,
day = "5",
doi = "10.1016/j.celrep.2022.110637",
language = "English",
volume = "39",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "1",
}