PHF10 subunit of PBAF complex mediates transcriptional activation by MYC

The PBAF complex, a member of SWI/SNF family of chromatin remodelers, plays an essential role in transcriptional regulation. We revealed a disease progression associated elevation of PHF10 subunit of PBAF in clinical samples of melanoma. We demonstrated that in melanoma cell lines, PHF10 interacts with MYC and facilitates the recruitment of PBAF complex to target gene promoters, therefore augmenting MYC transcriptional activation of genes involved in the cell cycle progression. Depletion of either PHF10 or MYC induced G1 accumulation and a senescence-like phenotype. Our data identify PHF10 as a pro-oncogenic mechanism and an essential novel link between chromatin remodeling and MYC-dependent gene transcription. Overall design: RNASeq assay was performed in A375 melanoma cells transfected with control siRNA (two replica), siRNA to PHF10 (four replica), or MYC (two replica). Knockdown of PHF10 and knockdown of MYC were performed as two independent experiments with appropriate controls.