Microarray analysis of human monocytic THP-1 cell treated with 1α,25-dihydroxyvitamin D3 or Trichostatin A and the combination of both

ABSTRACT: The nuclear hormone 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) regulates its target genes via activation of the transcription factor vitamin D receptor (VDR) far more specifically than the chromatin modifier trichostatin A (TsA) via its inhibitory action on histone deacetylases. We selected the thrombomodulin gene locus with its complex pattern of three 1α,25(OH)2D3 target genes, five VDR binding sites and multiple histone acetylation and open chromatin regions as an example to investigate together with a number of reference genes, the primary transcriptional responses to 1α,25(OH)2D3 and TsA. Transcriptome-wide, 18.4% of all expressed genes are either up- or down-regulated already after a 90 min TsA treatment; their response pattern to 1α,25(OH)2D3 and TsA sorts them into at least six classes. TsA stimulates a far higher number of genes than 1α,25(OH)2D3 and dominates the outcome of combined treatments. However, 200 TsA target genes can be modulated by 1α,25(OH)2D3 and more than 1000 genes respond only when treated with both compounds. The genomic view on the genes suggests that the degree of acetylation at transcription start sites and VDR binding regions may determine the effect of TsA on mRNA expression and its interference with 1α,25(OH)2D3. Our findings may have implications on dual therapies using chromatin modifiers and nuclear receptor ligands. All conditions are performed in triplicate: one time point with TsA treatment and vehicle control and one time point with TsA, 1α,25-dihydroxyvitamin D3, the combination of both and vehicle

ORGANISM(S): Homo sapiens

SUBMITTER: Sami Heikkinen 

PROVIDER: E-GEOD-36323 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress