title: Basic nuclear processes affected by histone acetyltransferases and histone deacetylase inhibitors.
abstract: OBJECTIVE
  The optimal balance between histone acetylation and deacetylation is important for proper gene function. Therefore, we addressed how inhibitors of histone-modifying enzymes can modulate nuclear events, including replication, transcription, splicing and DNA repair.
  
  
  METHODS
  Changes in cell signaling pathways upon treatment with histone acetyltransferases and/or histone deacetylase inhibitors were studied by cDNA microarrays and western blots.
  
  
  RESULTS
  We analyzed the effects of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) and the histone acetylase inhibitor MG149. SAHA altered the expression of factors involved in DNA replication complexes, basal transcription and the spliceosome pathway. DNA repair-related genes, including Rad51, Rad54 and BRCA2, were significantly downregulated by SAHA. However, MG149 had no effect on the investigated nuclear processes, with the exception of the spliceosome network and Sestrins, involved in DNA repair.
  
  
  CONCLUSIONS
  Based on our results, we propose that the studied epigenetic drugs have the distinct potential to affect specific cell signaling pathways depending on their respective molecular targets.
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Královopolská 135, 612 65, Brno, Czech Republic.
authors.forename: Soňa
authors.initials: S
authors.lastname: Legartová
authors.forename: Lenka
authors.initials: L
authors.lastname: Stixová
authors.forename: Hynek
authors.initials: H
authors.lastname: Strnad
authors.forename: Stanislav
authors.initials: S
authors.lastname: Kozubek
authors.forename: Nadine
authors.initials: N
authors.lastname: Martinet
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Dekker
authors.forename: Michal
authors.initials: M
authors.lastname: Franek
authors.forename: Eva
authors.initials: E
authors.lastname: Bártová
mesh_terms: D000107:Acetylation / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects; D024682:BRCA2 Protein / Q000235:genetics; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism; D004265:DNA Helicases; D004260:DNA Repair / Q000187:drug effects; D004268:DNA-Binding Proteins; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D020014:K562 Cells; D016328:NF-kappa B / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000235:genetics; D051135:Rad51 Recombinase / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D017381:Spliceosomes / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D000077337:Vorinostat
chemical_list: D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D004268:DNA-Binding Proteins; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D016328:NF-kappa B; D009687:Nuclear Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D000077337:Vorinostat; D012313:RNA; D051548:Histone Acetyltransferases; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; D004265:DNA Helicases; C103532:RAD54L protein, human