Post-translational modification (PTM) on histones plays important roles in regulating all DNA-dependent processes, including transcription and replication, by modulating the accessibility of DNA and recruiting protein factors to chromatin. PTMs on histones include phosphorylation, ubiquitination, ADP-ribosylation, O-GlcNAcylation, methylation and acetylation. The acetylation of lysine residues in histones is catalyzed by enzymes called histone acetyltransferases (HATs). Other than histones, many non-histone substrates have also been identified for HATs, adding another layer of complexity to their biological roles. Our lab is interested in understanding the functions of HATs and the mechanisms underlying their roles, and we are currently focusing on the Drosophila HAT Enok. Enok is a homolog of human MOZ, a key regulator of hematopoiesis and involved in leukemia, and is important for neuroblast proliferation and stem cell maintenance. Given that the protein complexes formed by Enok/MOZ are highly conserved between Drosophila and human, we are interested in using Drosophila as a simple and great genetic model to dissect the regulations and roles of Enok/MOZ.
Currently, we are pursuing two topics:
- The roles of Enok in cell cycle regulation through acetylating non-histone targets.
- The transcriptional roles of Enok in germline stem cell maintenance.