Basic nuclear processes affected by histone acetyltransferases and histone deacetylase inhibitors

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.

Changes in cell signaling pathways upon treatment with histone acetyltransferases and/or histone deacetylase inhibitors were studied by cDNA microarrays and western blots.

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.

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.