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Sodium butyrate-induced upregulation of p18INK4C gene affects K562 cell G0/G1 arrest and differentiation

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Abstract

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 p18INK4C mRNA and protein levels were upregulated during K562 cell erythroid differentiation induced by NaBu. Moreover, the NaBu activation of p18INK4C was dependent on the integrity of Sp1 clusters in the promoter. NaBu caused hyperacetylation of histones H3 and H4 on endogenous p18INK4C promoter and enhanced binding of transcription factor Sp1 in vivo. Also, overexpression of p18INK4C in K562 cells resulted in G0/G1 arrest and partial erythroid differentiation. Our results suggested that NaBu-mediated p18INK4C regulation played a role in cell cycle arrest and erythroid differentiation in K562 cells.

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Abbreviations

CDK:

Cyclin-dependent kinase

ChIP:

Chromatin immunoprecipitation

CKI:

Cyclin-dependent kinase inhibitor

HAT:

Histone acetyltransferase

HDAC:

Histone deacetylase

NaBu:

Sodium butyrate

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Acknowledgments

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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Authors and Affiliations

  1. Key Laboratory of Molecular Epigenetics of MOE, Institute of Genetics and Cytology, Northeast Normal University, Changchun, 130024, China

    Lin Li, Ye Zhang, Jiang Tan, Hui Huang, Baiqu Huang & Jun Lu

  2. Department of Biology, Guangdong Medical College, Dongguan, 523808, China

    Guoping Zhang

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  1. Lin Li
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  2. Guoping Zhang
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  3. Ye Zhang
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  7. Jun Lu
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Correspondence to Jun Lu.

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L. Li and G. Zhang contributed equally to this work.

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Li, L., Zhang, G., Zhang, Y. et al. Sodium butyrate-induced upregulation of p18INK4C gene affects K562 cell G0/G1 arrest and differentiation. Mol Cell Biochem 319, 9–15 (2008). https://doi.org/10.1007/s11010-008-9870-x

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  • DOI: https://doi.org/10.1007/s11010-008-9870-x

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