| Suberoylanilide hydroxamic acid induces limited changes in the transcriptome of primary CD4+ T cells. | |
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MedLine Citation:
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PMID: 23221426 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article |
Journal Detail:
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Title: AIDS (London, England) Volume: 27 ISSN: 1473-5571 ISO Abbreviation: AIDS Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2012-12-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8710219 Medline TA: AIDS Country: England |
Other Details:
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Languages: eng Pagination: 29-37 Citation Subset: IM; X |
Affiliation:
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aDepartment of Medicine, University of California San Diego, La Jolla bVeterans Affairs San Diego Healthcare System, San Diego cDepartment of Pathology, University of California San Diego, La Jolla, California, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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