FAD24, a Regulator of Adipogenesis, is Required for the Regulation of DNA Replication in Cell Proliferation

Abstract

A novel gene, factor for adipocyte differentiation 24 (fad24), promotes adipogenesis by controlling DNA replication early on during a stage referred to as mitotic clonal expansion (MCE). MCE is considered distinct from the proliferation of pre-confluent cells, so we investigated the role of fad24 in the process. First, the expression of fad24 was examined in pre-confluent and post-confluent 3T3-L1 preadipocytes, NIH-3T3 fibroblasts, and C2C12 myoblasts. fad24 was strongly expressed in the pre-confluent cells. The knockdown of fad24 by RNA interference impaired the ability of the pre-confluent cells to proliferate. Moreover, bromodeoxyuridine labeling and chromatin immunoprecipitation experiments indicated that the knockdown inhibited DNA synthesis by preventing the recruitment of histone acetyltransferase binding to ORC1 (HBO1), a component of the pre-replicative complex, to origins. fad24 plays positive roles in the proliferation of pre-confluent cells as well as adipogenesis.