Emerging role of the MORF/MRG gene family in various biological processes, including aging.

Cellular senescence is the dominant phenotype over immortality. In our studies to identify senescence-related genes, we cloned Morf4, which induced senescence in a subset of tumor cells. Morf4 is a member of a family of seven genes, and Morf-related genes (Mrg) on chromosomes 15 (Mrg15) and X (MrgX) are also expressed. In contrast to MORF4, MRG15 and MRGX are positive regulators of cell division. All three proteins interact with histone deacetylases and acetyltransferases, suggesting that they function in regulation of chromatin dynamics. Mrg15 knockout mice are embryonic lethal, and mouse embryonic fibroblasts derived from Mrg15 null embryos proliferate poorly, enter senescence rapidly, and have impaired DNA repair compared to the wild type. Mrg15 null embryonic neural stem and progenitor cells also have a decreased capacity for proliferation and differentiation. Further studies are needed to determine the function of this gene family in various biological processes, including neural stem and progenitor cell aging.