Retinoblastoma binding protein 2 (RBP2) and differentiation

摘要

During differentiation, RBP2 contributes to the role of the pRB tumor suppressor protein as a critical co-ordinator of cell-cycle exit and differentiation; however, how it regulates dependent genes is unknown. RBP2 and 3 homologs in mammals form the JARID1 protein family, and there are single orthologs in fly, worm, and fungi. RBP2 contains several domains, such as JmjC and PHD, which have been recently described in proteins with histone demethylase activity. To gain insight into transcriptional regulation by RBP2, we have identified RBP2 target genes using genome-wide location analysis. Surprisingly, we found that RBP2 target genes frequently encode proteins of mitochondrion and DNA-binding factors. In monocytic cells, many of the RBP2 targets are important in haematopoiesis. Interestingly, in differentiated cells, RBP2 represses genes involved in mitosis, many of which have been shown to be targets of the E2F transcription factor. Genes involved in the regulation of chromatin assembly and disassemblysignificantly changed in expression in RBP2 depleted cells (both induced and decreased), suggesting that regulation at the level of chromatin is advanced during RBP2-induced differentiation. These results represent an important step toward understanding of how RBP2 regulates gene expression. This work was supported in part by a grant from the American Chemical Society, Illinois Division.