Document Detail


Suberoylanilide hydroxamic acid induces limited changes in the transcriptome of primary CD4(+) T cells.
MedLine Citation:
PMID:  23221426     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To assess the off-target effects of the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA) in human primary CD4 T cells.
DESIGN: A pharmacologically relevant concentration (340 nmol/l) of SAHA was shown to significantly increase histone hyperacetylation by 24 h and this length of treatment was selected to determine its impact on gene expression in primary CD4 T cells.
METHODS: Illumina Beadchips for microarray gene expression analysis were used to analyze differential gene expression between cells treated or not with SAHA with a paired analysis using multivariate permutation tests. Gene ontology, biological pathway and protein interaction network analyses were used to identify the higher order biological processes affected by SAHA treatment.
RESULTS: Modest modulation by SAHA was observed for 1847 genes with 80% confidence level of no more than 10% false positives. A thousand genes were upregulated by SAHA and 847 downregulated. Pathways and gene ontologies overrepresented in the list of differentially expressed genes included Glycolysis/Gluconeogenesis, tRNA Modification, and the Histone Acetyltransferase Complex. Protein interaction network analysis revealed that transcription factor c-Myc, which was downregulated by SAHA treatment at the mRNA level, interacts with a number of SAHA-responsive genes.
CONCLUSIONS: The effects on transcription by SAHA were sufficiently modest to support trials to activate HIV replication as part of an eradication strategy. SAHA did not appear to modulate proliferative or apoptotic processes to a great extent, which might impact the ability of patients to eradicate the virus reservoir following activation by HDACi treatment.
Authors:
Nadejda Beliakova-Bethell; Jin X Zhang; Akul Singhania; Vivian Lee; Valeri H Terry; Douglas D Richman; Celsa A Spina; Christopher H Woelk
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  AIDS (London, England)     Volume:  27     ISSN:  1473-5571     ISO Abbreviation:  AIDS     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-12-10     Completed Date:  2013-06-17     Revised Date:  2013-08-30    
Medline Journal Info:
Nlm Unique ID:  8710219     Medline TA:  AIDS     Country:  England    
Other Details:
Languages:  eng     Pagination:  29-37     Citation Subset:  IM; X    
Affiliation:
Department of Medicine, University of California San Diego, La Jolla CA 92093-0679, USA. nbeliako@ucsd.edu
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects
CD4-Positive T-Lymphocytes / drug effects*,  metabolism
Cell Proliferation / drug effects*
Female
Gene Expression Regulation, Viral / drug effects
HIV-1 / drug effects*
Histone Deacetylase Inhibitors / pharmacology*
Humans
Hydroxamic Acids / pharmacology*
Male
Real-Time Polymerase Chain Reaction
Transcriptome / drug effects*
Virus Replication / drug effects
Grant Support
ID/Acronym/Agency:
2T32AI007384-21A1/AI/NIAID NIH HHS; AI007384/AI/NIAID NIH HHS; AI080193/AI/NIAID NIH HHS; AI096113/AI/NIAID NIH HHS; AI36214/AI/NIAID NIH HHS; I01 BX001160/BX/BLRD VA; P01 AI080193/AI/NIAID NIH HHS; P30 AI036214/AI/NIAID NIH HHS; T32 AI007384/AI/NIAID NIH HHS; U19 AI096113/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Histone Deacetylase Inhibitors; 0/Hydroxamic Acids; 149647-78-9/vorinostat
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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