These are linked to aberrant gene expression, in particular over an entire topologically-associated domain including part of the HOXD cluster. The chimeric protein assembles a mega-complex harboring both NuA4/TIP60 and PRC2 activities and leads to mislocalization of chromatin marks in the genome. In this study, we characterize the fusion protein produced by the EPC1- PHF1 translocation. While NuA4/TIP60 is a co-activator that acetylates chromatin and loads the H2A.Z histone variant, PHF1 is part of the Polycomb repressive complex 2 (PRC2) linked to transcriptional repression of key developmental genes through methylation of histone H3 on lysine 27.

Recent studies have identified highly recurrent chromosomal translocations in patients with Endometrial Stromal Sarcomas (ESS) and Ossifying FibroMyxoid Tumors (OFMT) leading to an in-frame fusion of PHF1 (PCL1) to six different subunits of the NuA4/TIP60 complex.

Chromosomal translocations frequently promote carcinogenesis by producing gain-of-function fusion proteins.

Solid converter pdf full mega