Nucleosomes are basis units of DNA packaging in eukaryotic cells. A core particle (mono-nucleosome) consists of a segment of DNA called core DNA (147 bp in length) wound around a histone octamer (Fig 1.). Histone octamers are made up of 2 copies of the the core histones H2A, H2B, H3, and H4. These mono-nucleosomes are connected by linker 80bp-long DNA. H1 histone, the so-called linker histone, binds to the linker DNA close to the entry and exit of the core DNA and is involved in chromatin compaction (Fig 1.). [Read more…]
A lot of efforts are made to identify potent and selective inhibitors for the demethylation reactions catalyzed by members of the JMJD2 and JARID1 protein families (1, 2). Both epigenetic eraser enzyme families have been discussed as potential cancer therapeutic targets. In this post, I will review the last releases regarding JMJD2 and JARID1 protein families for assay development and drug discovery applications.
A lot of antibodies that have been raised against modified Histones, e.g. methylated or acetylated histones, do not seem to have been tested for their specificity. Antibodies against mono-methylated lysines should, for instance, not recognize di- or tri-methylated sites. Or totally different sites which might be methylated as well. Eglehofer et al. reported about the specificity of > 200 antibodies against 57 different Histone modifications and found that more than 25% failed in specificity tests (Nat Struct Mol Biol 18.1, 91-3 ). In their paper they advised rigorous testing and provided an Antibody Validation Database.
Epigenetic modifications target DNA and Histone proteins.
One of the roles of Epigenetics is to drive cellular differentiation from totipotent Stem cells to fully differentiated cell types, by regulating gene expression through patterns of modifications that differ according to the cell type and the cell status. This means that the patterns may significantly differ between stem cells, germ cells, and differentiated cells.
It has been found that cancer cells often differ in regard to specific Epigenetic modification sites too. Thus, epigenetic enzymes are considered as potential pharmaceutical drug targets or biomarkers, and quite some effort is made to define drugable targets.
In this post, I’d like to take a look at Histone modifications, and especially histone modifying enzmes (writers). Later on, in further posts I’ll be focusing on enzymes which recognize specific modifications (readers), and those that erase modification from histones (erasers). [Read more…]