Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Specific inhibition of p300-HAT alters Global Gene Expression and Repress HIV replication

ABSTRACT: Reversible acetylation of histone and nonhistone proteins plays pivotal role in cellular homeostasis. Dysfunction of histone acetyltransferases (HATs) leads to several diseases including cancer, neurodegenaration, asthma, diabetes, AIDS and cardiac hypertrophy. We describe the synthesis and characterization of a set of p300-HAT specific small molecule inhibitors from a natural nonspecific HAT inhibitor, garcinol, which is highly toxic to cells. We show that the specific inhibitor selectively represses the p300-mediated acetylation of p53 in vivo. Furthermore, inhibition of p300-HAT down regulates several genes but significantly a few important genes are also upregulated. Remarkably, these inhibitors were found to be nontoxic to T cells, inhibit histone acetylation of HIV infected cells and consequently inhibit the multiplication of HIV. Keywords: Response to Inhibition of p300-HAT The total RNA was isolated from control and treated cells using TRIZOL (Invitrogen) method. The Micromax direct labeling kit, MPS502 (PerkinElmer) was used to synthesize the labeled cDNA from 70 ug of total RNA and further process the hybridized cDNA on the array. All the steps were carried out according to manufacturerâs instructions (www.perkinelmer.com/lifesciences). The array slides were scanned immediately by PerkinElmer Scan array Gx Microarray scanner. The Scan array software (PerkinElmer) was used for grid wise normalization of array images. Four arrays were used with at least two biological treatments of cells and dye swap experiments were included in the final analysis. The data was analysed by GeneSpring GX and Biointerpreter software from Genotypic Technology, Bangalore. The differential expression was considered if the Log 2 mean of at least -1 for the down regulated genes and +1 for the upregulated genes. We considered only the genes that were reproducible from all four replicates.

ORGANISM(S): Homo sapiens

SUBMITTER: Ashok Reddy

PROVIDER: E-GEOD-7818 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Specific inhibition of p300-HAT alters global gene expression and represses HIV replication.

Mantelingu K K Reddy B A Ashok BA Swaminathan V V Kishore A Hari AH Siddappa Nagadenahalli B NB Kumar G V Pavan GV Nagashankar G G Natesh Nagashayana N Roy Siddhartha S Sadhale Parag P PP Ranga Udaykumar U Narayana Chandrabhas C Kundu Tapas K TK

Chemistry & biology 20070601 6

Reversible acetylation of histone and nonhistone proteins plays pivotal role in cellular homeostasis. Dysfunction of histone acetyltransferases (HATs) leads to several diseases including cancer, neurodegenaration, asthma, diabetes, AIDS, and cardiac hypertrophy. We describe the synthesis and characterization of a set of p300-HAT-specific small-molecule inhibitors from a natural nonspecific HAT inhibitor, garcinol, which is highly toxic to cells. We show that the specific inhibitor selectively re ...[more]

PMID: 17584612

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Dataset Information

Specific inhibition of p300-HAT alters Global Gene Expression and Repress HIV replication

Publications

Specific inhibition of p300-HAT alters global gene expression and represses HIV replication.

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