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KMID : 0613820170270101104
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Journal of Life Science
2017 Volume.27 No. 10 p.1104 ~ p.1110
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Histone H3K4 Methyltransferase SET1A Stimulates the Adipogenesis of 3T3-L1 Preadipocytes
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Kim Seon-Hoo
Jung Myeong-Ho
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Abstract
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SET1A is a histone H3K4 methyltransferase that catalyzes di- and trimethylation of histone H3 at lysine 4 (H3K4). Mono-, di-, and trimethylations on H3K4 (H3K4me1, H3K4me2, and H3K4me3, respectively) are generally correlated with gene activation. Although H3K4 methylation is associated with the stimulation of adipogenesis of 3T3-L1 preadipocytes, it remains unknown whether SET1A plays a role in the regulation of adipogenesis of 3T3-L1 preadipocytes. Here, we investigated whether SET1A regulates 3T3-L1 preadipocytes’ adipogenesis and characterized the mechanism involved in this regulation. SET1A expression increased during 3T3-L1 preadipocytes’ adipogenesis. Consistent with the increased SET1A expression, the global H3K4me3 level had also increased on day 2 after the induction of adipogenesis in 3T3-L1 adipocytes. SET1A knockdown using siRNA in 3T3-L1 preadipocytes inhibited 3T3-L1 preadipocytes’ adipogenesis, as assessed by Oil Red O staining and the expression of adipogenic genes, indicating that SET1A stimulates the adipogenesis of 3T3-L1 preadipocytes. SET1A knockdown inhibited the cell proliferation of 3T3-L1 cells during mitotic clonal expansion (MCE) via downregulation of the cell cycle gene cyclin E1, as well as the DNA synthesis gene, dihydrofolate reductase. Furthermore, SET1A knockdown repressed peroxisome proliferator-activated receptor gamma (PPARγ) expression during the late stage of adipogenesis. These results indicate that SET1A stimulates MCE and PPARγ expression, which leads to the promotion of 3T3-L1 preadipocytes’ adipogenesis.
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KEYWORD
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Adipogenesis, histone methylation, mitotic clonal expansion, peroxisome proliferator- activated receptor γ, SET1A
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