Sodium butyrate-induced upregulation of p18 INK4C gene affects K562 cell G0/G1 arrest and differentiation
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Histone deacetylase inhibitor sodium butyrate (NaBu) can induce G0/G1 arrest and erythroid differentiation in K562 cells, but the molecular mechanisms underlying this process are unclear. Here we show that both p18 INK4C mRNA and protein levels were upregulated during K562 cell erythroid differentiation induced by NaBu. Moreover, the NaBu activation of p18 INK4C was dependent on the integrity of Sp1 clusters in the promoter. NaBu caused hyperacetylation of histones H3 and H4 on endogenous p18 INK4C promoter and enhanced binding of transcription factor Sp1 in vivo. Also, overexpression of p18 INK4C in K562 cells resulted in G0/G1 arrest and partial erythroid differentiation. Our results suggested that NaBu-mediated p18 INK4C regulation played a role in cell cycle arrest and erythroid differentiation in K562 cells.
Keywordsp18INK4C Sodium butyrate K562 erythroid differentiation Sp1
Cyclin-dependent kinase inhibitor
We thank Dr. Blais (Centre Hospitalier Universitaire de Quebec, Canada) for providing plasmids. This work was supported by grants from The National Basic Research Program of China (2005CB522404, 2006CB910506), the Program for Changjiang Scholars and Innovative Research Team (PCSIRT) in Universities (IRT0519), and the National Natural Science Foundation of China (30771232, 30671184).
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