They expected that yeast genetically engineered to carry fewer copies of certain
histone genes than normal or control yeast would have chromatin changes that would result in the yeast living less than controls.
(11) These HDACIs possess specific structural components that trigger diverse functions like interruption in the cell cycle, angiogenesis, and immunomodulation by acting on
histone and non-histone proteins.
In this research study, Celine Tiffon examines the effects of the differentiating
histone deacetylase inhibitor Trichostatin A (TSA) in human pancreatic cancer cell lines, representing different tumor grades.
In addition to cytosine methylation, post-translational modifications taking place in the
histone subunits composing the
histone octamer also contribute to the definition of gene expression patterns.
"Conceptually, we could use the modification, which is the methylation of adenosine residue, as a 'code' in mRNA to target
histone modifications to turn gene on or off," Zhao said.
Histone deacetylase inhibitors have been observed to enhance apoptosis of cancer cells induced by several chemotherapeutic agents including gemcitabine [43,48-53].
Although
histone proteins play an important role in DNA transcription, the participation of HATs and HDACs that form part of the transcription initiation complex with transcription factors and regulate
histone proteins has not been fully investigated in the brain.
Histone acetylation is preferentially carried out on specific lysine: for instance,
histone H3 is mainly acetylated in positions 9, 14, 18, and 23, while the lysine of
histone H4 that are preferentially acetylated are in positions 5, 8, 12, and 16.
Huang and Akbarian found an average 8-fold deficit in repressive chromatin-associated DNA methylation at GAD1 promoters in patients with schizophrenia [30] and it has been shown that
histone 3 (H3), one of the
histone proteins, was particularly dysregulated in schizophrenia patients [31].
The adding or removing of
histone marks is carried out by a group of enzymes named (1) "writers," responsible for adding ("writing") different epigenetic marks such as HAT (
histone acetyltransferase), which adds acetyl groups to
histone tails, (2) "erasers," responsible for the removal of epigenetic marks of the
histone, such as
histone deacetylases (HDACs) or
histone demethylases (HDMs), and (3) "readers," whose function is to recognize the different epigenetic marks added in the
histones.
Acetylation and deacetylation of
histones are controlled by
histone acetyltransferases (HAT) and
histone deacetylases (HDACs), respectively.