Developmentally regulated GTP binding protein 2 (DRG2) and Nup107 are associated with epigenetic regulation via H2A.Z on promoter regions of specific genes in MCF7 breast cancer cells

Abstract

Background: Epigenetic changes are critical events in breast cancer development. The regulation of epigenetic marks is orchestrated by DNA methylation, modifications of canonical histones, and incorporation of histone variants. A histone variant of H2A.Z was recently reported to be associated with breast cancer progression. However, the physiological function of H2A.Z in breast cancer has yet to be revealed. We previously identified genetic interactions between H2AvD (Drosophila H2A.Z) and DRG2 by means of Drosophila screening. Results: We herein focused on identifying new factors associated with DRG2 in order to reveal the epigenetic impact of H2A.Z on breast cancer. Initially, in a series of protein purification assays with a Drosophila cell line, we identified Nup107, a nuclear pore complex protein, as one of the factors interacting with DRG2. In addition, RWD domain containing 1 (RWDD1), GCN1 like protein 1 (GCN1L1), eukaryotic translation initiation factor 4B (eIF4B), and argininosuccinate lyase (ASL) were co-purified. Next, employing chromatin immunoprecipitationmicroarray analysis on the human breast cancer cell line MCF7, we revealed that H2A.Z, DRG2, and Nup107 co-occupy the promoter regions of 1,947 genes. In the common genes showing co-occupation with these three factors, the largest category, which included 871 genes, was found to consist of ‘alternative splicing variants’. This result and the factors co-purified suggest that H2A.Z, DRG2, and Nup107 co-regulate mRNA splicing as well as nuclear export and translation. Conclusions: Further analysis focusing on the biological functions of DRG2 and Nup107 would facilitate elucidating the epigenetic impact of H2A.Z on breast cancer development.