English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

The nuclear hormone 1α,25-dihydroxyvitamin D(3) (1α,25(OH)(2)D(3) or 1,25D) 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 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)(2)D(3) 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)(2)D(3) and TsA sorts them into at least six classes. TsA stimulates a far higher number of genes than 1α,25(OH)(2)D(3) and dominates the outcome of combined treatments. However, 200 TsA target genes can be modulated by 1α,25(OH)(2)D(3) 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)(2)D(3). Our findings hold true also for other HDAC inhibitors and may have implications on dual therapies using chromatin modifiers and nuclear receptor ligands.

nucleic acids research

Chromatin acetylation at transcription start sites and vitamin D receptor binding regions relates to effects of 1α,25-dihydroxyvitamin D3 and histone deacetylase inhibitors on gene expression