The Human Bromodomain Family
Development of drugs that target epigenetic signaling mechanisms is a new and exciting strategy for the treatment of cancer. Epigenetic processes including chemical modifications to DNA and also to the histone proteins that package the DNA in chromatin play a central role in gene expression and regulation. One of the most frequently occurring modifications is the acetylation of lysine residues (Kac) and deregulation of this process has been associated with many common diseases, such as cancer, diabetes, obesity and Alzheimer's disease. Historically, most therapeutic development has focused on the group of enzymes that “write” and “erase” acetylation marks on histones. But more recently, epigenetic “reader” proteins that sense the presence of these epigenetic marks are also being explored as novel therapeutic targets.
The Bromodendrogram TREEspot™ phylogenetic tree is an enhanced rendering of human bromodomains and describes the relationships between members of this protein class. The main dendrogram is organized into eight different subfamilies designated by Roman numerals (I - VIII) based on alignments of bromodomains as described by Filippakopoulos et al. (Cell 149:214-231, 2012).