Within cells, DNA is condensed into chromatin by histone proteins. Covalent post-translational modifications of histones such as methylation, acetylation, and ubiquitination of basic histone residues regulate the accessibility of gene loci activating or repressing their transcription. The combination of histone modifications across the genome creates an “epigenetic landscape” that maintains coordinated expression of transcriptional programs required for cell fate determination during development.
Dysregulation of histone methylation leads to aberrant gene expression that is a driving force behind the development of various human cancers. Hence, the roles of methyltransferases in human disease remain an area of intense research especially relating to drug discovery pursuing the myriad of potential epigenetic targets . . .
Garrett S. Gibbons, Amarraj Chakraborty, Sierrah M. Grigsby, Afoma C. Umeano, Chenzhong Liao, Omar Moukha-Chafiq, Vibha Pathak, Bini Mathew, Young-Tae Lee, Yali Dou, Stephan C. Schürer, Robert C. Reynolds, Timothy S. Snowden, Zaneta Nikolovska-Coleska, Identification of DOT1L inhibitors by structure-based virtual screening adapted from a nucleoside-focused library, European Journal of Medicinal Chemistry, Volume 189, 2020, 112023, ISSN 0223-5234, https://doi.org/10.1016/j.ejmech.2019.112023.