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

Summary 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 .