Polyisoprenylated Benzophenone, Garcinol, a Natural Histone Acetyltransferase Inhibitor, Represses Chromatin Transcription and Alters Global Gene Expression

Balasubramanyam, Karanam and Altaf, M and Varier, Radhika A and Swaminathan, V and Ravindran, Aarti and Sadhale, Parag P and Kundu, Tapas K (2004) Polyisoprenylated Benzophenone, Garcinol, a Natural Histone Acetyltransferase Inhibitor, Represses Chromatin Transcription and Alters Global Gene Expression. In: Journal of Biological Chemistry, 279 (32). pp. 33716-33726.

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Abstract

Histone acetylation is a diagnostic feature of transcriptionally active genes. The proper recruitment and function of histone acetyltransferases (HATs) and deacetylases (HDACs), is a key regulatory step for gene expression and cell cycle. Functional defects of either of these enzymes may lead to several diseases, including cancer. HATs and HDACs thus are potential therapeutic targets. Here we report that garcinol, a polyisoprenylated benzophenone derivative from Garcinia indica fruit rind, is a potent inhibitor of histone acetyltransferases p300 (IC$_{50}$~7\mu M) and PCAF (IC$_{50}$~5\mu M) both in vitro and in vivo. The kinetic analysis shows that it is a mixed type of inhibitor with an increased affinity for PCAF as compared to p300. HAT activity dependent chromatin transcription was strongly inhibited by garcinol, whereas transcription from DNA template was not affected. Furthermore, it was found to be a potent inducer of apoptosis, and it alters(predominantly down regulates) the global gene expression in HeLa cells.

Item Type:	Journal Article
Publication:	Journal of Biological Chemistry
Publisher:	American Society for Biochemistry and Molecular Biology
Additional Information:	Copyright for this article belongs to American Society for Biochemistry and Molecular Biology.
Keywords:	p300;PCAF;Histone acetyltransferase (HAT);Histone Deacetylase (HDAC);Chromatin modification;Transcription;Apoptosis
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	28 Oct 2004
Last Modified:	19 Sep 2010 04:16
URI:	http://eprints.iisc.ac.in/id/eprint/2184

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