title: Suberoylanilide hydroxamic acid induces limited changes in the transcriptome of primary CD4(+) T cells.
abstract: OBJECTIVE
  To assess the off-target effects of the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA) in human primary CD4 T cells.
  
  
  METHODS
  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.affiliation: Department of Medicine, University of California San Diego, La Jolla CA 92093-0679, USA. nbeliako@ucsd.edu
authors.forename: Nadejda
authors.initials: N
authors.lastname: Beliakova-Bethell
authors.forename: Jin X
authors.initials: JX
authors.lastname: Zhang
authors.forename: Akul
authors.initials: A
authors.lastname: Singhania
authors.forename: Vivian
authors.initials: V
authors.lastname: Lee
authors.forename: Valeri H
authors.initials: VH
authors.lastname: Terry
authors.forename: Douglas D
authors.initials: DD
authors.lastname: Richman
authors.forename: Celsa A
authors.initials: CA
authors.lastname: Spina
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Woelk
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008297:Male; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects; D000077337:Vorinostat
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D000077337:Vorinostat