Sodium butyrate-induced upregulation of p18( INK4C ) gene affects K562 cell G (0)/G (1) arrest and differentiation.
Histone deacetylase inhibitor sodium butyrate (NaBu) can induce G(0)/G(1) 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 G(0)/G(1) 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.
Li
Lin
L
Institute of Genetics and Cytology, Northeast Normal University, Changchun, China.
Zhang
Guoping
G
Zhang
Ye
Y
Tan
Jiang
J
Huang
Hui
H
Huang
Baiqu
B
Lu
Jun
J
D002087:Butyrates / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D050763:Cyclin-Dependent Kinase Inhibitor p18 / Q000096:biosynthesis*; D041905:Erythroid Cells / Q000166:cytology / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects*; D006657:Histones / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D020218:Response Elements; D016192:Resting Phase, Cell Cycle / Q000187:drug effects*; D016329:Sp1 Transcription Factor / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
D002087:Butyrates; C493971:CDKN2C protein, human; D050763:Cyclin-Dependent Kinase Inhibitor p18; D006657:Histones; D016329:Sp1 Transcription Factor