Development of a versatile screening platform for the identification of small-molecule ligands for reader proteins of the post-translational methylation

Abstract

Covalent Post Translational Modifications (PTMs) of histone proteins are introduced and removed by the ‘writer’ and ‘eraser’ enzymes, respectively. These modifications are recognized by highly specific binding domains, the so-called ‘reader’ proteins, which are thought to mediate epigenetic signalling. Misregulation of these proteins often leads to abnormal gene expression patterns that are more frequently linked to human diseases. In comparison to writers and erasers, readers have been less intensively pursued so far as therapeutic targets, especially with regard to methylation. To date, different biochemical and biophysical techniques are reported to assess the binding of new putative modulators of methyl readers. Nevertheless, given the intrinsic limitations each technique encompasses, reliable data can be obtained using a combination of methods. .. [edited by the Author]