The role of DOT1L in the maintenance of leukemia gene expression

Chromatin based (Epigenetic) mechanisms have been shown to play important roles in the regulation of gene expression during tumorigenesis and development. Mouse modeling suggests the methyltransferase DOT1L as a potential therapeutic target for MLL-rearranged leukemia. Epigenomic profiling indicates an abnormal H3K79me2 pattern on MLL-fusion targeted genes, but the molecular mechanism underlying this epigenetic dependency is not well understood. In this review, we will discuss recent advances in understanding the epigenetic mechanisms governed by DOT1L in the maintenance of gene expression. We will highlight the structural basis of chromatin targeting of DOT1L through its cofactors and the role of DOT1L in repelling transcription repressive complexes during leukemia development.