HDIs are currently being investigated as chemosensitizers for cytotoxic chemotherapy or radiation therapy, or in association with DNA methylation inhibitors based on in vitro synergy. Isoform selective HDIs which can aid in elucidating role of individual HDAC isoforms have been developed. HDAC inhibitors have effects on non-histone proteins that are related to acetylation. HDIs can alter the degree of acetylation of these molecules and, therefore, increase or repress their activity. For the four examples given above (see Function) on HDACs acting on non-histone proteins, in each of those instances the HDAC inhibitor Trichostatin A (TSA) blocks the effect. HDIs have been shown to alter the activity of many transcription factors, including ACTR, cMyb, E2F1, EKLF, FEN 1, GATA, HNF-4, HSP90, Ku70, NFκB, PCNA, p53, RB, Runx, SF1 Sp3, STAT, TFIIE, TCF, YY1. The ketone body β-hydroxybutyrate has been shown in mice to increase gene expression of FOXO3a by histone deacetylase inhibition. Histone deacetylase inhibitors may modulate the latency of some viruses, resulting in reactivation. This has been shown to occur, for instance, with a latent human herpesvirus-6 infection. Histone deacetylase inhibitors have shown activity against certain Plasmodium species and stages which may indicate they have potential in malaria treatment. It has been shown that HDIs accumulate acetylated histone H3K9/H3K14, a downstream target of class I HDACs. See also Histone acetyltransferase (HAT) Histone deacetylase inhibitor Histone methyltransferase (HMT) Histone-modifying enzymes RNA polymerase control by chromatin structure References External links Animation at Merck EC 3.5.1