BRG 1 promotes survival of UV ‐irradiated melanoma cells by cooperating with MITF to activate the melanoma inhibitor of apoptosis gene

• Published in: Pigment cell and melanoma research Vol. 26; no. 3; pp. 377 - 391
• Main Authors: Saladi, Srinivas V., Wong, Philip G., Trivedi, Archit R., Marathe, Himangi G., Keenen, Bridget, Aras, Shweta, Liew, Zi‐Qi, Setaluri, Vijayasaradhi, de la Serna, Ivana L.
• Format: Journal Article
• Language: English
• Published: 01-05-2013
• ISSN: 1755-1471; 1755-148X
• DOI: 10.1111/pcmr.12088

Microphthalmia‐associated transcription factor (
MITF
) is a survival factor in melanocytes and melanoma cells.
MITF
regulates expression of antiapoptotic genes and promotes lineage‐specific survival in response to ultraviolet (
UV
) radiation and to chemotherapeutics.
SWI
/
SNF
chromatin‐remodeling enzymes interact with
MITF
to regulate
MITF
target gene expression. We determined that the catalytic subunit,
BRG
1, of the
SWI
/
SNF
complex protects melanoma cells against
UV
‐induced death.
BRG
1 prevents apoptosis in
UV
‐irradiated melanoma cells by activating expression of the melanoma inhibitor of apoptosis (
ML
‐
IAP
). Down‐regulation of
ML
‐
IAP
compromises
BRG
1‐mediated survival of melanoma cells in response to
UV
radiation.
BRG
1 regulates
ML
‐
IAP
expression by cooperating with
MITF
to promote transcriptionally permissive chromatin structure on the
ML
‐
IAP
promoter. The alternative catalytic subunit,
BRM
, and the
BRG
1‐associated factor,
BAF
180, were found to be dispensable for elevated expression of
ML
‐
IAP
in melanoma cells. Thus, we illuminate a lineage‐specific mechanism by which a specific
SWI
/
SNF
subunit,
BRG
1, modulates the cellular response to
DNA
damage by regulating an antiapoptotic gene and implicate this subunit of the
SWI
/
SNF
complex in mediating the prosurvival function of
MITF
.