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Gene Targeting
A major challenge facing the development of PI3K-targeted pharmaceutical agents is the lack of patient-relevant, in vitro model systems. Studies into the function of oncogenic mutations are commonly carried out in cell line panels that are mutant or wild-type for the gene of interest, however interpretation of these studies can be confounded by additional genetic differences between each cell line background, calling into question the reliability of the results.
Epigenomics
Histone deacetylases (HDACs) are a class of enzymes that remove acetyl groups from ε-N-acetyl lysine amino acids on histones and other proteins. The removal of acetyl groups serves to increase the positive charge of histone tails, encouraging binding between histones and the DNA backbone, and preventing transcription.
Epigenetics
Post-translational modifications of histones are among the epigenetic mechanisms that can affect chromatin structure and function. Disruption of epigenetic processes can lead to altered gene expression and malignant cellular transformation.
Epigenetics
Several assay methods have been developed for quantifying the activity of histone deacetylases (HDACs and sirtuins), histone methyltransferases (HMTs), and histone demethylases (HDMs). These include radioactive assays, enzymelinked immunoassays (ELISA), mass spectrometry, and enzyme-coupled detection of fluorescent peptides or reaction co-products (e.g.
Epigenetics
Post-translational modifications of histone proteins play an important part in a wide array of cellular processes including regulation of gene transcription, DNA repair, cell cycle, and metabolism control. For instance, transcriptional activation is associated with acetylation of Histone H3 on residues K9 and K14, and methylation on K4.
Epigenetics
In eukaryotes, the covalent modification of histones has a crucial role in chromatin architecture and plays an important part in a plethora of cellular processes, from chromatin remodeling and transcriptional regulation, to DNA repair and cell cycle control. While histone acetylation is generally associated to an open chromatin state and transcriptional activation, methylation of histones has been related to either activating or repressive functions.
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