Journal
EXPERIMENTAL CELL RESEARCH
Volume 318, Issue 3, Pages 177-186Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2011.11.010
Keywords
Histone deacetylases; Multidrug resistance; P-gp; Sp1
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Funding
- Longyi Team
- National Base of TCM Clinical Research [LYTD-05]
- 111 Project [B07023]
- National Nature Science Foundation of China [81173224]
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Recent reports have showed that histone deacetylase (HDAC) inhibitor resulted in multidrug resistance (MDR) to other chemotherapeutic agents. However, the molecular mechanisms of Class I HDACs on MDR regulation are poorly understood. In this study, HDAC1 and HDAC2 acted as enhancers to intensify the chemosensitivities of anti-cancer drugs via reducing the expression levels of P-gp, MRP1 and MRP2. Furthermore, the dissociation of HDAC1 and HDAC2 led to transcriptional regulation of P-gp expression via the recruitment of p300, PCAF and NF-Y to the P-gp promoter region, which subsequently increased the level of the active gene marker, hyperacetylated histone H3. In parallel, selective inhibition of HDAC1 and HDAC2 induced the recruitment of p300, PCAF, NF-Y via acetylation of Sp1. Thus, our findings showed HDAC1 and 2 regulated P-gp expression through dynamic changes in chromatin structure and transcription factor association within the promoter region. Crown Copyright (C) 2011 Published by Elsevier Inc. All rights reserved.
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