Title:Histone and Non-Histone Targets of Dietary Deacetylase Inhibitors
VOLUME: 16 ISSUE: 7
Author(s):Eunah Kim, William H. Bisson, Christiane V. Löhr, David E. Williams, Emily Ho, Roderick H. Dashwood and Praveen Rajendran
Affiliation:Center for Epigenetics & Disease Prevention, 2121 West Holcombe Blvd., Houston, TX 77030, USA.
Keywords:Acetylation, Diet, Epigenetics, Phytochemicals, HDAC, Non-histone.
Abstract:Acetylation is an important, reversible post-translational modification affecting histone and non-histone proteins
with critical roles in gene transcription, DNA replication, DNA repair, and cell cycle progression. Key regulatory
enzymes include histone deacetylase (HDACs) and histone acetyltransferases (HATs). Overexpressed HDACs have been
identified in many human cancers, resulting in repressed chromatin states that interfere with vital tumor suppressor functions.
Inhibition of HDAC activity has been pursued as a mechanism for re-activating repressed genes in cancers, with
some HDAC inhibitors showing promise in the clinical setting. Dietary compounds and their metabolites also have been
shown to modulate HDAC activity or expression. Out of this body of research, attention increasingly has shifted towards
non-histone targets of HDACs and HATs, such as transcriptions factors, hormone receptors, DNA repair proteins, and cytoskeletal
components. These aspects are covered in present review, along with the possible clinical significance. Where
such data are available, examples are cited from the literature of studies with short chain fatty acids, polyphenols, isoflavones,
indoles, organosulfur compounds, organoselenium compounds, sesquiterpene lactones, isoflavones, and various
miscellaneous agents. By virtue of their effects on both histone and non-histone proteins, dietary chemopreventive agents
modulate the cellular acetylome in ways that are only now becoming apparent. A better understanding of the molecular
mechanisms will likely enhance the potential to more effectively combat diseases harboring altered epigenetic landscapes
and dysregulated protein signaling.
