FAD24, a regulator of adipogenesis, is required for the regulation of DNA replication in cell proliferation.
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.
Johmura
Yoshikazu
Y
Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Aichi, Japan.
Osada
Shigehiro
S
Nishizuka
Makoto
M
Imagawa
Masayoshi
M
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics* / Q000502:physiology*; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics* / Q000502:physiology*; D015152:Blotting, Northern; D001973:Bromodeoxyuridine / Q000494:pharmacology; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation; D002843:Chromatin / Q000235:genetics; D004261:DNA Replication / Q000187:drug effects / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D051548:Histone Acetyltransferases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology*; D051738:Origin Recognition Complex / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000963:Antimetabolites; D050976:Basic-Leucine Zipper Transcription Factors; D018797:Cell Cycle Proteins; D002843:Chromatin; C502215:Noc3l protein, mouse; D009687:Nuclear Proteins; D051738:Origin Recognition Complex; D051548:Histone Acetyltransferases; D001973:Bromodeoxyuridine