Chromatin is the physiological template of our genome. As such, elaborate mechanisms have evolved to introduce meaningful variation into chromatin for purposes of altering gene expression and other important biological processes.
Constellation has a long standing history in targeting multiple classes of chromatin regulators that fall into various ‘chromatin regulatory pathways’. Histone lysine methylation is controlled by a large family of histone lysine methyltransferases (writers), two histone lysine demethylase families (erasers) and multiple classes of histone methyl-lysine binding proteins (readers). Methylation at individual histone lysine residues on nucleosomes in the vicinity of transcriptional start sites and at distal regulatory elements can have profound impact on the transcriptional output. Depending on the location of the lysine residue and the degree of methylation (mono-, di-, tri-) at a given residue histone lysine methylation can either promote or suppress gene expression. Histone acetylation is controlled by a histone acetyltransferase superfamily (writers), three classes of histone deacetylases (erasers) and the bromodomain-containing protein family (readers). Acetylation of histone lysine residues alters the charge distribution of histone proteins and loosens the interaction between histone proteins and DNA, thereby facilitating transcription. Chromatin remodeling is controlled by multiple families of ATP-dependent chromatin remodeling complexes that alter chromatin in a non-covalent manner, sliding nucleosomes along the DNA axis, lift DNA off the histone protein surface and replace canonical histones with variant histone proteins.