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

doi:10.1016/j.celrep.2022.110637

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

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

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.

Original language	English (US)
Article number	110637
Journal	Cell Reports
Volume	39
Issue number	1
DOIs	https://doi.org/10.1016/j.celrep.2022.110637
State	Published - Apr 5 2022
Externally published	Yes

Keywords

ARID2
BAF
CP: Cancer
PBAF
SWI/SNF
chromatin
invasion
melanoma
transcription factors

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.celrep.2022.110637

Cite this

Carcamo, S., Nguyen, C. B., Grossi, E., Filipescu, D., Alpsoy, A., Dhiman, A., Sun, D., Narang, S., Imig, J., Martin, T. C., Parsons, R., Aifantis, I., Tsirigos, A., Aguirre-Ghiso, J. A., Dykhuizen, E. C., Hasson, D., & Bernstein, E. (2022). Altered BAF occupancy and transcription factor dynamics in PBAF-deficient melanoma. Cell Reports, 39(1), Article 110637. https://doi.org/10.1016/j.celrep.2022.110637

Carcamo, S, Nguyen, CB, Grossi, E, Filipescu, D, Alpsoy, A, Dhiman, A, Sun, D, Narang, S, Imig, J, Martin, TC, Parsons, R, Aifantis, I, Tsirigos, A, Aguirre-Ghiso, JA, Dykhuizen, EC, Hasson, D & Bernstein, E 2022, 'Altered BAF occupancy and transcription factor dynamics in PBAF-deficient melanoma', Cell Reports, vol. 39, no. 1, 110637. https://doi.org/10.1016/j.celrep.2022.110637

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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",

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doi = "10.1016/j.celrep.2022.110637",

language = "English (US)",

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TY - JOUR

T1 - Altered BAF occupancy and transcription factor dynamics in PBAF-deficient melanoma

AU - Carcamo, Saul

AU - Nguyen, Christie B.

AU - Grossi, Elena

AU - Filipescu, Dan

AU - Alpsoy, Aktan

AU - Dhiman, Alisha

AU - Sun, Dan

AU - Narang, Sonali

AU - Imig, Jochen

AU - Martin, Tiphaine C.

AU - Parsons, Ramon

AU - Aifantis, Iannis

AU - Tsirigos, Aristotelis

AU - Aguirre-Ghiso, Julio A.

AU - Dykhuizen, Emily C.

AU - Hasson, Dan

AU - Bernstein, Emily

PY - 2022/4/5

Y1 - 2022/4/5

N2 - 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.

AB - 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.

KW - ARID2

KW - BAF

KW - CP: Cancer

KW - PBAF

KW - SWI/SNF

KW - chromatin

KW - invasion

KW - melanoma

KW - transcription factors

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SN - 2211-1247

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Altered BAF occupancy and transcription factor dynamics in PBAF-deficient melanoma

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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