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Role for Class I histone deacetylases in multidrug resistance.
Exp Cell Res. 2012 Feb 1;318(3):177-86
Authors: Xu Y, Jiang Z, Yin P, Li Q, Liu J
Abstract
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.
PMID: 22154511 [PubMed - indexed for MEDLINE]
Source: http://www.ncbi.nlm.nih.gov/PubMed/22154511?dopt=Abstract