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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3-L1 Cells
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Adipocytes / metabolism
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Adipogenesis / genetics*
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Adipogenesis / physiology*
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Animals
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Antimetabolites / pharmacology
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Basic-Leucine Zipper Transcription Factors / genetics*
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Basic-Leucine Zipper Transcription Factors / physiology*
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Blotting, Northern
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Bromodeoxyuridine / pharmacology
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Cell Cycle Proteins
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Cell Differentiation / drug effects
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Cell Differentiation / physiology
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Cell Proliferation*
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Chromatin / genetics
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DNA Replication / drug effects
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DNA Replication / physiology*
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Fluorescent Antibody Technique
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Histone Acetyltransferases / metabolism
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Mice
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Mice, Knockout
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Myoblasts / drug effects
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Myoblasts / metabolism
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NIH 3T3 Cells
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Nuclear Proteins / genetics*
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Nuclear Proteins / physiology*
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Origin Recognition Complex / metabolism
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RNA Interference
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Reverse Transcriptase Polymerase Chain Reaction
Substances
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Antimetabolites
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Basic-Leucine Zipper Transcription Factors
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Cell Cycle Proteins
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Chromatin
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Noc3l protein, mouse
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Nuclear Proteins
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Origin Recognition Complex
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Histone Acetyltransferases
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Bromodeoxyuridine